Lungs from fetal guinea pigs of 61 +/- 3 days of gestation were supported in vitro for 3 h, and lung liquid secretion rates were measured by a dye dilution technique based on Blue Dextran 2000. Ten preparations that had received no treatment showed an average secretion rate of 1.12 +/- 0.28 mL.kg-1 body weight.h-1 during the first hour, and there were no significant changes over the following 2 h. In studies of 54 fetal lungs, furosemide, bumetanide, control ethanol carrier, or saline alone were placed in the supporting medium during the middle hour of the 3-h incubations (ABA design). Furosemide at 10(-3) M reduced secretion 83.4 +/- 16.8%; at 10(-4) and 10(-5) M it produced smaller reductions. Bumetanide at 10(-3) M usually produced reabsorption (129.9 +/- 23.0% reduction), at 10(-4) M it reduced secretion 30.9 +/- 11.8%, but at 10(-5) M it was ineffective. Control carrier and saline were without effect. The ability of the loop diuretics to produce reabsorption of fluid in some preparations suggests the unmasking of an active reabsorptive process. The results also suggest that lung liquid secretion in the fetal guinea pig, as in the sheep, is dependent on a Na+ and Cl- cotransport system.