Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally. We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes. The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar. Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery. Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth. The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account. Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size. The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.