We infused forskolin in 30% ethanol or 30% ethanol systemically in seven chronically catheterized near-term sheep to determine the response of ovine uterine musculature to cyclic adenosine monophosphate stimulation. Maternal and fetal arterial pressure, fetal venous pressure, intrauterine pressure, and uterine electromyogram activity were monitored continuously. Prostaglandin E2 was infused at a delivery rate that caused a minimal 5 mm Hg increase in intrauterine pressure with definite contraction-like pressure spikes and associated uterine electromyogram activity. Forskolin (10 mg in 30% ethanol) or ethanol (vehicle) was then infused for 20 minutes. The prostaglandin E2 challenge was repeated 3 minutes later and again every 30 minutes over a 2 1/2-hour period. Data were analyzed by repeated measures analysis of variance. Infusion of ethanol (n = 2) had no apparent effect on either the intrauterine pressure or the uterine electromyogram response to prostaglandin E2 challenge. Forskolin infusion (n = 5) caused an attenuation of the intrauterine pressure response to prostaglandin E2 for 93 minutes. This effect was greatest 33 minutes after the infusion ended when the integrated pressure signal was 37% of the initial prostaglandin E2 response. The forskolin infusion had no effect on uterine electromyogram response to prostaglandin E2. We conclude that forskolin causes an uncoupling of excitation from contraction in the intact near-term ovine uterus.