The central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT₁ receptor mediate diuresis and natriuresis, whereas both 5-HT₂ and 5-HT₃ mediate antidiuresis and antinatriuresis. Recently, 5-HT₁ receptors are further subdivided into many subtypes, and central 5-HT_1A subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of 5-HT_1B subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective 5-HT_1B agonist in doses ranging from 8 to 750μg/kg icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with 250μg/kg icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective 5-HT₁ blocker. Both ketanserin and MDL 72222, selective 5-HT₂ and 5-HT₃ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, 5-HT_1A blocker, affect the TFMPP effects. These observations suggest that central 5-HT_1Breceptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.