A placebo-controlled, randomized study of the effect of a 10-day infusion of morphine (MOR) upon fetal survival and fetal breathing movements was done in late gestation lambs. MOR infusion at a rate of 3 mg.hr-1 did not affect fetal survival or the response of fetal breathing movements to hypercapnia. Chronic exposure to MOR increased the height of the integrated diaphragmatic electromyogram signal (IDIA), respiratory drive and inspiratory effort during periods of eucapnia. Respiratory drive was determined by the product of IDIA height and breathing frequency, and inspiratory effort was the quotient of IDIA height divided by inspiratory time. These effects may be related to accumulation of morphine-3-beta-D-glucuronide. Higher doses of MOR, 10 (n = 3) and 30 (n = 1) mg.hr-1, caused seizures and decreased fetal survival.