The purpose of this study was to determine whether physical stimulation is stressful to the ovine fetus, as judged from physiologic changes that are similar to those reported for other stressors (such as hypoxia); whether any stress response could be blocked by clinically used doses of fentanyl; and whether fentanyl alone had any potentially deleterious physiologic effects in the fetus. We investigated the effect of fentanyl analgesia on the cardiovascular and endocrine response to cutaneous electrical stimulation in the late gestation (>125 days) ovine fetus (n=7 fetuses). Chronically implanted catheters and blood flow probes were used to measure fetal arterial blood pressure, heart rate, carotid and femoral blood flow, pH, Po(2), Pco(2), lactate, cortisol, and beta-endorphin levels before, during, and for 1 hour after 5 minutes of cutaneous electrical stimulation to the lip, forelimb, and abdomen, in a crossover design. Clinically used 30 or 150 microg doses of fentanyl (which approximated 10 or 50 microg/kg estimated fetal weight) or saline solution were given intravenously to the fetus 2 minutes before stimulation. When compared with the control, stimulation caused a significant rise in fetal heart rate (P=.003; mean maximal rise, 48.6+/-14.0 beats/min, 0-10 minutes after the start of stimulation) but caused no change in any other parameters studied. Neither dose of fentanyl attenuated the changes in heart rate that were observed in response to stimulation alone. Fentanyl alone significantly increased fetal heart rate, carotid blood flow, and lactate and cortisol levels and significantly decreased pH and Po(2). Cutaneous electrical stimulation in the fetal sheep causes an increase in heart rate, which fentanyl does not block. Fentanyl itself has significant effects on the cardiovascular and endocrine system, which might adversely affect the fetus.