The renal vascular effect of tertatolol and analogues was investigated in isolated rat kidney perfused at constant flow in an open circuit with Krebs-Henseleit solution after vascular tone had been reestablished by bolus injections of serotonin or other vasoconstrictor drugs. Against serotonin-induced vasoconstriction, (+/-)tertatolol (3 X 10(-7)-3 X 10(-5) M) evoked concentration-dependent relaxation (IC 50 = 4.6 +/- 0.4 X 10(-6) M), (-)tertatolol was more active than the racemic and (+)tertatolol was less active. (+/-)Tertatolol competitively antagonized serotonin-induced renal constriction (pA2 = 5.6 +/- 0.2). Tertatolol metabolites (4-OH tertatolol, 4,5-di-OH tertatolol, and sulfoxy tertatolol) were inactive. (+/-)Sotalol and (+/-)nadolol, were also inactive in this model and (-)bunolol induced renal vasodilatation only at concentrations 40 times higher than (-)tertatolol. The renal response to tertatolol was not linked to release of prostaglandins or dopamine or to interaction with the dopamine receptor, since neither indomethacin nor SCH 23390 affected tertatolol-induced renal vasodilatation. Tertatolol also elicited relaxation of N6-cyclohexyladenosine-induced renal vasoconstriction (34 +/- 7% relaxation at 3 X 10(-5) M) but was inactive when renal vascular tone was raised by prostaglandin F2 alpha, angiotensin II, or neuropeptide Y in the presence of norepinephrine.