The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors.