Europeans had domestic animals (horses, pigs, cows, sheep, dogs, chickens), meaning that they had acquired resistance to the many diseases that animals bring with them. The Americas had few animals that were capable of domestication, thus natives did not domesticate animals and did not acquire resistance through close exposure. When Europeans first arrived with their animals, it entailed natives first exposure to these pathogens.

http://www.amazon.com/dp/0393317552 Guns, Germs, and Steel by Jared M. Diamond does a great job of explaining this in detail, and not just in the North Americas, but examples throughout the world.

It boils down to a few basic ideas

1: Native american's had no real concept of quarantine. If someone was sick, the extended family would take care of them. In turn the extend family would become infected, and infect the rest of the village/tribe as they travelled.

2: Europeans lived in cities with much greater population densities. Their immune systems were much more accustomed to dealing with a large variety of infectious agents. Whereas the native americans live is small homogenous villages. With very little exposure to outside influences, other than other tribes/villages.

I think the most important takeaway was actually that Europe and Asia have huge swaths of land at roughly similar latitudes, so that it was easy for crops and domesticated animals to spread east/west. Those allowed for more intense agriculture, and along with them went diseases.

Here's the wikipedia page, which actually goes into more depth:

http://en.wikipedia.org/wiki/Guns,_Germs,_and_Steel

Agreed, Diamond's most salient points are 1) the latitudinal axis of Eurasia compared to the longitudinal one of the Americas and 2) the role of domesticated animals as disease vectors. The stuff about pre-Columbians not paying attention to quarantine is quite frankly rubbish (both because Europeans had no modern notions of quarantine either, and because it's impossible to make a blanket statement about how two continents-worth of civilizations conceptualized disease), as is the stuff about lack of urbanization (at least in the context of present-day Mexico and Peru, which indeed did have urbanization on a scale to rival Europe).

A personal pet peeve of mine is that Alfred Crosby wrote about this stuff in the 1970s (The Columbian Exchange) and the 1980s (Ecological Imperialism) but Diamond gets all the credit for it because he successfully repackaged it for more popular audiences, without adding much.

It's hypothesized that syphilis was carried back to Europe by returning sailors. It doesn't work like smallpox, but it caused a major problem for hundreds of years.

Here are some more reasons that haven't been mentioned yet. Keep in mind this is speculative on my part.

1. I read somewhere that the probable migration of native Americans over the ice-age land bridge between Asia and Alaska meant that the peoples lived for generations in climates too cold for new pathogens to evolve to infect humans. I guess because there weren't enough animals in the area with a sufficient genetic similarity to humans. So by the time people migrated south to warmer climates, they had no natural immunity to the diseases common in Europe.

Another way to look at this is that Europe is closer to Africa. Africa is where most human diseases come from, because it's where humans evolved, and the diseases got to co-evolve with them.

2. Native Americans had better hygiene. And by that I mean they bathed regularly. Europeans were, by most accounts, sort of disgusting. They lived mostly in a cold climate (remember it was colder back then), and saw nakedness as unacceptable pretty much ever. They mostly just didn't bathe. Perhaps this is why the earlier failed Viking settlements had less of an effect on the native American population.

Europeans of the era bathed regularly as well, and often even communally. Nudity wasn't as rare as many make it out to be.

And they washed their faces, teeth, and hands at least daily.

http://www.gallowglass.org/jadwiga/herbs/baths.html

I'm not sure how to reconcile this with what I read in the book Lies My Teacher Told Me, which contradicts the source you've given here.

Well, the source I link to pulls from a variety of sources, many of which are in the bibliography at the bottom of the page. And that source matches with pretty much all the other actual medieval history books I've read.

EDIT- It occurred to me that early New England colonists might have been different from the general European population, being more strict in their living style based on religious beliefs. That might explain it, but I've never looked into Puritan bathing habits.

American populations had been cut off from mixing for millennia. Europeans kept moving around, sharing bugs and having plagues that killed off millions. Then rebounding and doing it again. Made for a more resistant population?

Less generally resistant, just more resistant to the particular witch's brew of diseases out of Europe itself (as one would expect). Remember, Syphilis tore up Europe when it came over from the Americas.

But that doesn't explain why the admittedly larger population of Americas didn't have their own brew to pass on to the explorers.

Density and less transportation to spread exciting things from further away?