1. Perfusion of the receptive field (RF) of C- or A delta-fiber nociceptors with nerve growth factor (NGF) in an in vitro preparation of the rat saphenous nerve with functionally attached skin induced a significant decrease in heat threshold without changing mechanical or cold sensitivity. 2. NGF-induced thermal sensitization was absent after saline perfusion and in skin taken from mast-cell depleted animals, hence confirming a role for mast cells in NGF-induced thermal hyperalgesia. 3. Neurotrophin-5 (NT-5) also induced a small but significant reduction in heat threshold without affecting mechanical sensitivity. It is speculated that NT-5 exerts its action either directly on the trkA receptor, as with NGF or alternatively through trkB receptors located on sympathetic efferents or on small diameter afferents.