The effect of the putative 5-HT1A agonists 8-OH-DPAT and ipsapirone and 5-HT1B agonists TFMPP and m-CPP on respiratory activity in rats has been examined. In chloral hydrate-anesthetized rats, respiratory counts were decreased in a dose-dependent manner by both TFMPP and m-CPP, with an ED50 of 0.30 mg/kg (1.1 mumol/kg) and 3.0 mg/kg (11.0 mumol/kg) respectively. In contrast, both 5-HT1A agonists tested, 8-OH-DPAT and ipsapirone, produced an increase in respiratory rate at all doses tested. Moreover, the TFMPP-induced decrease in respiratory rate was antagonized by 8-OH-DPAT. The 5-HT2 antagonist ketanserin had no effect on the TFMPP-induced decrease in respiratory activity. However, methylsergide (5-HT1/5-HT2 antagonist) and (-)-cyanopindolol (5-HT1B antagonist) antagonized the TFMPP-induced respiratory rate decrease. The results of these experiments, coupled with the predominant presence of 5-HT1B receptors in the lower brainstem, pons, and medulla, as established by autoradiography studies, suggest a possible involvement of the 5-HT1B receptor subtype in the control of respiratory mechanisms, especially those involved in respiratory rhythmicity.