The concentrations of the somatomedins (SMs) insulin-like growth factors I and II (SM-C/IGF-I and IGF-II) were measured by RIA in six normal and seven insulin-dependent diabetic pregnant women and their infants at delivery. SM-C/IGF-I and IGF-II levels in the two groups of women were similar. Maternal IGF-II concentrations correlated with maternal hemoglobin AIc levels (r = 0.68) and infant birth weight ratios (actual birth weight/expected 50th percentile sex-corrected birth weight for gestation age; r = 0.54). SMC/IGF-I and IGF-II levels in umbilical plasma in infants of diabetic mothers did not differ from those in control infants, but were lower than the corresponding maternal values. In contrast, umbilical plasma levels of C-peptide immunoreactivity were significantly elevated in the infants of diabetic mothers (2.25 +/- 1.85 (+/-SD) vs. 0.34 +/- 0.15 pmol/ml; P less than 0.01). The infant birth weight ratio was logarithmically correlated with the umbilical plasma C-peptide immunoreactivity (r = 0.78). SM levels were also measured by radioreceptor assay in five normal and five hyperinsulinemic rhesus monkey fetuses. When chronic hyperinsulinemia was produced by continuous SC infusion of insulin in the fetal rhesus monkey, the fetal birth weight ratio was also found to be logarithmically correlated with the fetal plasma insulin concentration (r = 0.81). The fetal SM peptide content was elevated only in the fetuses with plasma insulin levels greater than 3000 microU/ml. The fetal weight gains in response to hyperinsulinemia in the human and rhesus are similar. Since fetal SM levels in the humans and monkeys were not significantly different in the two groups, our data suggest that insulin plays the predominant role in stimulating human and subhuman primate excess fetal weight gain of the infant of the diabetic mother during the latter part of gestation.