I've had this problem intermittently for a couple years now. It's very aggravating, especially because I've never figured out for certain why it happens. I found that using a proxy can "fix" it, which is both worrying and confusing in itself, but of course the free proxy I've used to test that was slow and not really a good solution for long-term problems. Luckily as I said, the problem is intermittent.

But it would seem the image host server just plain stops responding to my IP for whatever reason now and then. Usually if I've been browsing the site for a few minutes and already looked at a number of images. (Or other media like vids/animations) Sometimes I wonder if its a timeout from too many successive requests, because I do tend to open several tabs of images at a time as I'm browsing. I could understand something like that to protect against DDS attacks or something, but just a few requests from a single user shouldn't trigger that, I would think.

The other alternatives are a problem with either my ISP or my router... both of which I kind of doubt, but who knows. And in any case I don't have this problem with any other sites so far. Just e621, and just the image server at that.