How many times will your knee bend on a heavy leg work out compared to running or cycling? could be cartlidge rub after a while the knee gets irritated, this would not happen with the weights as you get breaks between sets. I think id try Nicks possible solution if this does not work then i think you may have a cartlidge problem. Have a look on this forum
http://www.runnersworld.co.uk you might find the answer.