Maternal administration of 2,5-dimethoxy-4-methyl-amphetamine (DOM) produced a dose-dependent increase in maternal and fetal arterial blood pressure and a fall in the heart rate. Maternal uterine artery blood flow was dramatically decreased following DOM administration, and the uterine vascular resistance increased. These responses were accompanied by fetal hypoxemia, combined metabolic and respiratory acidosis, hypertension and bradycardia. The changes in the blood flow and the vascular resistance produced by DOM were always smaller in fetal umbilical arteries than in the maternal uterine artery. Maternal administration of ketanserin (1 mg/kg) 30 minutes prior to the administration of DOM inhibited maternal and fetal cardiovascular and arterial blood gas responses to DOM. The effects of DOM on the uterine and umbilical vasculature were further investigated by the use of isolated tissues. Both serotonin (5-hydroxytryptamine, 5-HT) and DOM produced potent vasoconstriction on the isolated ovine uterine and umbilical vessels. Contractions to 5-HT and DOM were effectively blocked by ketanserin. MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) did not antagonize the 5-HT induced vasoconstriction on the uterine and umbilical vessels. The vasoconstriction produced by 8-OH-DPAT (8-hydroxy-dipropylaminotetralin), 2-methyl-5-HT, 2-MPP (1-(-methoxyphenyl) piperazine), TFMPP (m-trifluoromethyl-phenylpiperazine) and mCPP (1-(3-chlorophenyl) piperazine) in the uterine and umbilical vessels was blocked by ketanserin. The variation in the sensitivity and the potency of the serotonergic agonists is primarily caused by the variation in their relative affinity for the 5-HT2 receptor and less so by their relative efficacy. Activation of [alpha]-adrenergic receptors is not involved in the responses produced by 5-HT in these vessels. 5-HT and DOM produced a concentration-dependent increase in Ca[superscript]2+ uptake by the uterine artery, which was effectively blocked by ketanserin and methiothepin but not by MDL 72222. D600 and nifedipine also blocked the Ca[superscript]2+ influx induced by 5-HT. Amrinone had no effect on 5-HT-induced Ca[superscript]2+ influx in the uterine artery.