We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45, delta of -0.047 mg, p = 0.004; period B, days 45 to 50, delta of -0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, delta of -0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, delta of -0.072 mg, p = 0.001; period E, days 45 to 55, delta of -0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level).(ABSTRACT TRUNCATED AT 250 WORDS)