Maternal serum α2-macroglobulin levels were measured twice, at approximately 18 and 30 weeks’ gestation, in 289 pregnant women who later delivered at or after 37 weeks. Levels were elevated as early as 18 weeks’ gestation in women destined to have a growth-retarded infant, and this elevation persisted through 30 weeks’ gestational age. Furthermore, levels were higher in white women than black, in smokers than in non-smokers, and in thin than in heavier women. When the effect of α2-macroglobulin on birth weight was evaluated in a multiple regression analysis adjusting for gestational age, race, body size, smoking, fetal sex, and a history of a low birth weight infant, high α2-macroglobulin levels were associated with a statistically significant decrease in birth weight. The effect was greater in women who smoked. This relationship did not appear to be associated with differences in serum zinc or hematocrit levels. © 1991 by The American College of Obstetricians and Gynecologists.