The amplitude of vocalization and the motor defense response evoked by painful electrical stimulation were recorded in unanesthetized guinea pigs submitted to topical application of 1.0 microgram/microliter carbachol to the area postrema. Carbachol was found to have an analgesic effect. A similar application of 3.0 micrograms/microliter 5-hydroxytryptamine (5-HT) also had an analgesic effect, whose duration, however, was only half that of carbachol and whose intensity was lower, although the latency of the response was 2 seconds for both drugs. When 100 micrograms/microliter lysergic acid was applied to the area postrema the results did not differ significantly from control values, with only a small tendency toward hyperalgesia being observed. The present results, taken together with those obtained with noradrenalin in a previous study, suggest that the rich endowment of neurotransmitters in the area postrema may indicate a polyvalent analgesic mechanism able to provide a finer regulation of analgesia.