The fetoscopic approach to fetal intervention is a promising minimally invasive technique for correcting congenital anomalies in utero. However, expansion of the amniotic cavity with CO2 to visualize the fetus causes fetal hypercarbia and acidosis. We assessed whether maternal hyperventilation during intrauterine CO2 insufflation could attenuate the fetal hypercarbic acidosis. Seven fetal lambs of 105 +/- 2 days (mean +/- SEM) gestation (term = 145 days) were instrumented with a carotid arterial catheter in utero. After 7 +/- 1 days of recovery, fetoscopic exposure was obtained with intrauterine insufflation of CO2 at 10 mmHg of intraamniotic pressure. After 30 min, the ewe was hyperventilated at a mean respiratory rate of 23/min for 30 min under continuous insufflation. The uterus was then deflated and following 1 hr of stabilization, and the same protocol of CO2 pneumometrium was repeated. Fetal and maternal arterial blood was sampled at baseline and at 15 min intervals. Fetal PaCO2 increased during 30 min of CO2 insufflation (50.8 +/- 2.8 vs. 72.3 +/- 5.0 mmHg, P < 0.01); however, this change was reversed (to 51.5 +/- 3.0 mmHg, P < 0.01) by 30 min of maternal hyperventilation. The fetus developed acidosis after 30 min of CO2 pneumometrium (pH 7.350 +/- 0.012 vs. 7.236 +/- 0.026, P < 0.01); this was also reversed (to 7.366 +/- 0.019, P < 0.01) by maternal hyperventilation. These results were reproducible during the second CO2 insufflation challenge. Fetal hypercarbic acidosis during fetoscopy with CO2 insufflation is reduced by maternal hyperventilation.