The objective of this study was to evaluate the physiologic consequences of a pneumoperitoneum (pneumo) to the midterm fetus in a pregnant sheep model. The performance of laparoscopic cholecystectomy (LC) during pregnancy is controversial. The primary concern regarding the safety of LC during pregnancy is the physiologic consequences of the CO2 pneumo to the fetus. Eight ewes with singlet pregnancies between 100 and 120 days of gestation were anesthetized and intubated. Carotid artery and internal jugular catheters were placed in the ewe and in the fetus. Two trocars were placed through the abdominal wall of the ewe and the abdomen was inflated with CO2 or N2O at 15 mmHg pressure for 90-120 min. Hemodynamic and blood gas data were obtained every 15 min before, during, and after the pneumo. In two ewes attempts were made to keep maternal Pco2 constant with hyperventilation. In two other animals the pneumo was increased stepwise in five mmHg increments to 25 mmHg. One fetus succumbed during the CO2 pneumo, but this animal appeared to be ill during the establishment of invasive monitoring. Fetal respiratory acidosis occurred, reproducibly, after establishment of CO2 pneumo but did not occur before insufflation or under N2O pneumo (P < 0.0001). Hemodynamic changes were minimal with all agents but it appeared that there a was greater prevalence of fetal tachycardia and hypertension during CO2 pneumo than during N2O pneumo. Alterations in ventilator settings based on maternal capnography resulted in late and incomplete correction of respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)