Pulmonary surfactant production, measured by the saturated phosphatidylcholine/sphingomyelin (SPC/S) ratio, is delayed in male rabbit fetuses at 26 to 28 days' gestation (Nielsen and Torday, Ped Res 14:459, 1979). We have observed that the SPC/S ratio in lung lavage (LL) of female fetuses is quantitatively related to the number of neighboring male fetuses, suggesting that the sex difference is hormone-dependent. Therefore, we administered DHT to pregnant rabbit does daily from the 12th postconceptional day. Doses of 25mg, 10mg and lmg/day were used to show a dose/response relationship. The fetuses were delivered on the 26th day. The fetal lungs were lavaged with 5 × 0.5ml aliquots of iced saline. Fetal sex was determined by inspection of the gonads. Phospholipids were extracted from LL, chromatographed and then measured by spectrodensitometry. All DHT doses eliminated the sex difference in the LL SPC/S ratio. Increasing doses of DHT correlated significantly with lower mean SPC/S ratios (p<.05). The DHT effect was apparently organ-specific since there was significant inhibition of fetal lung alkaline phosphatase activity with no detectable effect on fetal duodenal alkaline phosphatase activity. This is the first evidence of a steroid hormone delaying pulmonary surfactant production. These findings suggest a hormonal basis for the known male disadvantage in the Respiratory Distress Syndrome of the newborn. Partially supported by a grant from the King Trust.