I don't know about billions, but I've personally witnessed an Excel spreadsheet for millions of dollars that was manually updated.

It was sent over an encrypted Symantec thingie (where it was processed on my side), but errors weren't uncommon, it was really hard to automate, and I did get to see people being over-(and under-)charged due to manual errors.

Edit: a sibling comment has a story about moving billions over a macro, not mere millions :) .

One place I worked, they processed and paid payroll twice one month because someone dropped the files again and the ESB dutifully picked them up and sent them. That was a $6m mistake, took them years to work out how to reclaim the money from the workers (unions involved, contract lawyers, you name it).

The JP Morgan Whale incident [1] was a classic recent example of huge amounts of cash being managed in spreadsheets.

[1] http://spreadserve.com/blog/entry/saving-the-whale-excel-spr...