OBJECTIVE To evaluate the effect of nitric oxide synthase activity inhibition on the fetal lamb umbilical artery flow velocity waveform. METHODS Five pregnant Corriedale cross ewes were operated on at 125-130 days' gestation. Fetal and maternal vascular catheters were inserted along with a Doppler flow meter cuff on the fetal common umbilical artery. Each fetus received a 40-minute intravenous (i.v.) infusion of N omega-nitro-D-arginine as a control, and then after a recovery period of 1 hour, a 40-minute i.v. infusion of N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase activity. Maternal and fetal heart rate, blood pressure, blood gases, and fetal umbilical artery flow velocity waveforms were recorded at basal time and after the 40-minute i.v. infusions. RESULTS There were no differences in fetal or maternal heart rate, blood pressure, or blood gases with the infusion of the nitric oxide synthase inhibitor N omega-nitro-L-arginine. However, N omega-nitro-L-arginine caused a significant increase (41%) in the fetal umbilical artery flow velocity waveform systolic to diastolic ratio (S/D) above the baseline levels. CONCLUSIONS Inhibition of nitric oxide synthase activity in the lamb fetoplacental circulation with N omega-nitro-L-arginine is associated with an increase in the umbilical artery S/D.