The isolated and perfused kidney of the spontaneously hypertensive rat (SHR) exhibits an increased vascular reactivity to serotonin when compared to normotensive Wistar-Kyoto (WKY) rats. Experiments were designed to determine the involvement of a prostanoid constricting factor in the augmented response to serotonin in the SHR kidney. Kidneys taken from male (12 months) SHR and WKY rats were studied in parallel and perfused with Tyrode's solution at constant, optimal flow rates. Vasoconstrictor response were recorded as increases in perfusion pressure. The dose-response curves to serotonin obtained in the SHR were shifted to the left compared to the WKY. Indomethacin decreased the responses to the smaller doses of serotonin in the SHR, but increased those to the higher doses of the monoamine in the WKY. The responsiveness to the monoamine was no longer significantly different in the two strains in the presence of the inhibitor of cyclooxygenase. Dazoxiben, an inhibitor of thromboxane synthetase, did not alter the responses to serotonin in either the WKY and SHR kidneys. These experiments suggest that a prostanoid, but not thromboxane A2, may play a role in the augmented response to serotonin in the kidney of aged SHR.