Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin injected fetuses (n=15), surfactant (S) fraction phosphatidylcholine (PC) and dis saturated phosphatidylcholine (DSPC) were significantly decreased (3.6 ± 0.1 nmol Pi/ mg tissue; p<0.001 and 2.8 ± 0.1 nmol/mg; p<0.025, respectively) as compared with their saline-injected controls (4.8 ± 0.2 and 3.3 ± 0.1 nmol/mg, respectively, n=19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 ± 0.13 µm2(n=72) versus 1.99 ± 0.14 µm2(n=129) p<0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 ± 1.0 Mg/mg, n=17) than in their controls (15.1 ±0.8 fig/mg, n=18; p<0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin injections: 4.3 ± 0.25 and 3.4 ± 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n=10) versus 5.7 ± 0.45 and 4.3 ± 0.3 nmol Pi/mg, respectively, in controls (n=10, p<0.05). In addition, PG was also decreased (0.24 ± 0.03 versus 0.40 ± 0.04 nmol Pi/mg, n=10; p<0.01), and in contrast with insulin injections, reductions of DSPC and PG were detectable in whole lung. However, glycogen content was unchanged by glucose infusion (13.7 ±1.0 µg mg, n=15 versus 14.0 ± 1.1 Mg/mg, n=20 in controls). In both models, the phospholipid composition of material recovered by lung lavage was unchanged. (Pediatr Res 21: 436-441,1987