Subcutaneous injection of dilute formalin induces pain in humans and behaviors indicative of pain in animals. The formalin test, which is based on these observations, is now widely used as a model of pain produced by tissue injury, but the neural mechanisms of pain and analgesia in this test have not been identified. Rats with transections of the brain rostral or caudal to the pons show behavioral reactions to formalin similar to those of normal rats, although the temporary abatement of pain 10-15 min after formalin is absent in transected animals. Doses of morphine that suppress the behavioral response to formalin in normal rats are not antinociceptive in the formalin test in decerebrate rats although sedation, catalepsy and inhibition of the tail-flick reflex still occur. These results suggest that the response to formalin is organized in the brain stem but the antinociceptive effect of morphine in this test is mediated by the diencephalon or forebrain.