In pithed rats, m-chlorophenylpiperazine (m-CPP) produced marked, dose-dependent (ED50 = 0.18 mumol) increases in mean arterial blood pressure which peaked within 1 minute and were sustained over 15 minutes. Two serotonin antagonists, metergoline and ritanserin, completely blocked the pressor responses to 2.5 mg/kg m-CPP in pithed adrenal demedullated rats, while alpha-adrenergic blockade by prazosin plus yohimbine was without effect, suggesting that the doubling in blood pressure produced by m-CPP was mediated via serotonin receptors within blood vessels. Somewhat smaller increases in blood pressure over baseline values were observed after m-CPP administration to conscious, freely moving rats. A small but statistically significant increase in heart rate peaked 5 minutes after m-CPP and also was blocked by metergoline but was only minimally affected by ritanserin or the prazosin-yohimbine combination. These results with m-CPP support other evidence for two or more separable effects of serotonergic agonists on the peripheral cardiovascular system.