I second what jhc said, your calves is where you will feel it as you adjust. Start out slow and with short runs, work up to faster and longer, you'll be fine, some discomfort along the way is normal. Just be sure that you're not having heel pain -- if you're heel striking in VFFs you're in big trouble. Make sure that your stride in VFFs is a little shorter than it would be in conventional althetic shoes, and that you are landing on your mid-/fore-foot.
Actually, I've been running short distances (1-2.5 miles or so) and doing most of my day-to-day walking in my VFF's for over 6 months now, and still, when I wore them on a 4.5 mile hike this Saturday....well, I'm still a little sore today, and it is all in my calves. I'm sure my calf muscles do a lot more work on those rocky, steep surfaces than they do on the sidewalks and flat gravel I'm usually on. I did actually bring a pair of backup conventional hiking shoes, but didn't feel at the time that I needed to switch to them. So it's definitely a normal thing, to feel it right there.
Edited to add: as a sidenote since you mentioned knee injury, I had zero knee pain on and after the hike, which I struggled with before I got into VFFs. I still haven't talked my husband into the idea of toe shoes, so he was hiking in conventional shoes, and he had considerable knee pain towards the end of the hike and the following day, something he doesn't normally struggle with like I used to. And for what it's worth, slightly achy/stretched calves feel a lot better and healthier than joint pain ever did.
Last edited by ErikaE; 08-08-2011 at 12:02 PM.
“The goal of life is to make your heartbeat match the beat of the universe, to match your nature with Nature.” -- Joseph Campbell