The fetal lung is an important site of fluid production and is postulated to serve a regulatory role in fetal fluid balance. To assess the role of atrial natriuretic factor on fetal lung liquid production, we studied the effect of intravenous atrial natriuretic factor infusion on tracheal fluid production in fetal sheep with chronic vascular and tracheal catheters. Ovine fetuses (mean gestation = 130 days +/- 1 day) received successive 40-minute intravenous infusions of increasing doses of synthetic fragment 1-28 atrial natriuretic factor (5, 25, and 100 ng/min.kg-1). In response to the 25 ng/min.kg-1 infusion, fetal tracheal fluid production decreased from 1.2 +/- 0.3 ml/10 min to 0.6 +/- 0.2 ml/10 min (p less than 0.05), and remained suppressed during the 100 ng/min.kg-1 infusion (0.5 +/- 0.2 ml/10 min). There was a significant inverse correlation between tracheal fluid production and fetal plasma atrial natriuretic factor levels (r = -0.61, p less than 0.001). Basal tracheal fluid sodium and potassium concentrations (147 +/- 1 mEq/L and 5 +/- 1 mEq/L) and osmolality (291 +/- 3 mOsm) did not change during the atrial natriuretic factor infusion periods. The observation that atrial natriuretic factor acts to decrease fetal lung fluid production suggests that atrial natriuretic factor may be important in the fetal adaptive response to extrauterine life.