BACKGROUND: Buspirone is a partial 5-HT1A receptor agonist. Animal studies have shown that modulation of serotoninergic transmission at the 5-HT1A receptor can induce analgesia in acute pain models. However, no studies have been published so far on the effects of serotonin receptor agonists on pain perception in humans. METHODS: The effects of buspirone (30 mg p.o.) on thermal sensory and pain thresholds were investigated in twelve female volunteers (26 +/- 2 yrs) in a prospective, randomized, double-blind, double-dummy, placebo-controlled study with morphine (10 mg i.v.) as positive control. RESULTS: Morphine significantly increased the heat pain detection threshold (DeltaT: placebo 1.0 degrees C and 1.3 degrees C, p < 0.05) at 60 minutes. Buspirone caused mild sedation in six participants at 60 minutes, but was without effect on any of the measured parameters. CONCLUSION: Buspirone in the maximal recommended dose was without significant effect on thermal pain. However, as it is only a partial agonist at the 5-HT1A receptor and also acts on other receptor types, the negative results of the present study do not rule out a possible analgesic effect of more specific 5-HT1A receptor agonists.