Adult CD-1 male mice were injected intravenously with 2.5 micrograms/g of highly purified murine NGF and then assessed for hot plate responding (52 degrees C) at 15, 30, 60, 180, and 360 min (repeated test) or at 30, 60, or 360 min (single test, i.e., exposure to hot plate only once). Control animals received cytochrome c (2.5 micrograms/g). In the repeated test, NGF produced hyperalgesia, increasing the number of jumps (particularly at 30 and 60 min postinjection), while in the single test the pain reaction of NGF-treated animals remained unaffected. Sensitization of C-fibers in the periphery or release of bioactive mediators from mast cells may account for NGF-induced changes in nociception.