Employing a sensitive competitive protein binding assay for NSILA (non-suppressible insulin-like activity), circulating levels of this somatomedin (SM) were measured throughout pregnancy, at parturition, and in fetal and newborn sera. Acid-dissociable serum NSILA (mean .+-. SE of the mean) in 57 women was significantly higher during pregnancy (1106 .+-. 46 .mu.U[units]/ml), than in 11 adult non-pregnant control subjects (844 .+-. 22 .mu.U/ml), but not correlated with week of gestation or with serum growth hormone (GH) or cortisol levels. At parturition, the NSILA concentration in 28 cord sera (598 .+-. 38 .mu.U/ml) was significantly less than in the corresponding maternal sera (1039 .+-. 63 .mu.U/ml). The NSILA levels in 23 premature newborns (370 .+-. 20 .mu.U/ml) and 8 small-for-gestational-age newborns (310 .+-. 46 .mu.U/ml) were significantly less than in 33 term newborns (494 .+-. 18 .mu.U/ml). Serum NSILA in 56 term and premature newborns exhibited a significant positive correlation with gestational age and birth weight but not with serum GH or cortisol levels. The maternal-fetal growth-promoting system is apparently a highly complex one in which NSILA levels both in maternal and fetal circulations appear to be under multifactorial control.