Previous evidence suggests that, in adult animals, nerve growth factor (NGF) can induce hyperalgesia, and may be an endogenous mediator in some persistent pain states. Here we have studied the effects of single intradermal injections of 50-500 ng of human recombinant NGF into the plantar skin of adult rat hindpaws. We found that doses of 250 ng and more produced a prolonged and stable thermal hyperalgesia to radiant heat. NGF did not produce overt pain behaviour as judged by the absence of paw licking or guarding of the injected paw. In animals subjected to surgical or chemical sympathectomy, by repeated systemic guanethidine treatments, the hyperalgesic effects of NGF were markedly reduced. We also found that NGF produced plasma extravasation in rat skin, using the Evan's blue method, with a dose dependency similar to that determined for hyperalgesia. Together, these findings suggest that NGF can lead to a rapid activation and sensitization of cutaneous nociceptors. However, these actions appear at least partly indirect, requiring the presence of normal sympathetic post-ganglionic terminals.