We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed cases of CO poisoning occurring during pregnancy between December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), car fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomographic findings consistent with ischemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehavioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P less than 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcome.