There's a city that sits on a river, the intersections of several well-traveled roads, and a large rail line (back when that was worth something; the city is kind of a blend of the early 1900's). It's thriving, as you'd expect.
I need to turn it into a near-ghost town, but without using disease, war, supply shortages, or anything that would make it extremely obvious why everyone left; it's important to the story that all characters involved have their own theory and no rumor is more likely than any other.
Ideally, the population would dwindle away to next-to-nothing in a seemingly natural manner, with even the local authorities preferring to commute to the area.
Once things get underway, I'm sure there would be reinforcing factors ("this place ain't what it used to be, I'm gettin' out" / "we're cutting back on how many trains we send past" / "gee, where'd all my friends go"), but I need something to get the migration started.
EDIT: I should have thought of this beforehand, but I've tied my SE account to the username I normally use on the Internet, which this will almost certainly be published under. I don't feel like I can risk selecting an answer here, but moreso, you guys all came up with some excellent stuff, with none of them superior to each other. Worldbuilding might not be a perfect fit for the Q&A "one accepted answer" format, after all. I voted up everything I thought fit the restrictions of the question as a small show of thanks. Cheers!