Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsive dorsal root ganglion (DRG) cells (<30 microns) maintained in dissociated cell culture (6-24 h). A second puff of capsaicin 10 min later always evoked a substantially smaller inward current than the initial puff (tachyphylaxis). Bath-application of NGF (2, 10 or 100 ng/ml) during the 10-min interval resulted in facilitation of the second response in a dose dependent manner in 67% of cells studied. NT-4/5 exerted similar effects but NT-3 did not. Ten minute pretreatment with NGF increased the initial response to capsaicin. We conclude that NGF acutely conditions the response to capsaicin via direct action on DRG cells. Since the capsaicin receptor (VR1) mediates noxious heat sensitivity of polymodal nociceptors, acute sensitization of the noxious heat response by NGF and NT-4/5 may involve a direct action on VR1.