We analyzed 205 diabetic women treated with insulin during pregnancy to assess the effects of several maternal factors on the development of fetal macrosomia. A total of 95 women were selected for study because they had clearly defined gestational criteria, two or more daytime glucose profiles during the third trimester, and no other complications known to affect fetal growth. The incidence of macrosomia was not found to increase significantly until the mean glucose concentration reached 130 mg/dl; macrosomia occurred in 65% of mothers with glucose values greater than or equal to 130 mg/dl compared with 27% in those with lower values. Other factors strongly associated with fetal macrosomia were maternal weight and insulin dosage. Multiple logistic analysis was performed to control for each risk factor and to obtain estimates of the relative risk for macrosomia. The risk of macrosomia was two times greater in women with mean glucose concentrations greater than or equal to 130 mg/dl, approximately threefold in women whose weight exceeded 80 kg, and one and one half times greater in women with insulin dosages more than 80 units/day. We conclude that several maternal factors in addition to glucose concentration play important roles in the development of fetal macrosomia among diabetic women and that the glucose concentration threshold for macrosomia may exceed 130 mg/dl.