A lot of it depends on your conditioning, as well. If you're only used to short, local jaunts, you're not just gonna hop on the bike and do 500 miles - not without some seriously sore repercussions the next day
Your health has an impact, too. My wife had 2 spinal surgeries 10 days apart in February, 2004. Last weekend, we went on a 400 mile 2-day trip from Leavenworth, Kansas into Nebraska on Saturday, stayed the night in Bellevue, Ne and then into Iowa, Missouri and back home to Kansas on Sunday. She still has some pretty serious nerve damage but we stopped about every 45 mins or so. The breaks really helped (so did the pool and hot tub at the hotel Saturday night!). It's the longest ride she's taken since the surgeries but we've worked up to it progressively.
I think the trick is to pace it out so that you're not rushing to get anywhere... let the road flow under you instead of you flying over the road