Maternal diabetes mellitus is complicated by fetal macrosomia and predisposes the offspring to diabetes, but recent evidence indicates that a low, not high, birthweight is associated with a higher incidence of Type 2 (non-insulin dependent) diabetes in adult life. To clarify the relationships between maternal glucose and insulin levels and birthweight, we measured oral glucose tolerance and neonatal weight in a large group (n = 529) of women during the 26th week of pregnancy. Women with gestational diabetes (n = 17) had more familial diabetes, higher pre-pregnancy body weight, and tended to have large-for-gestational-age babies. In contrast, women with essential hypertension (n = 10) gave birth to significantly (p <0.01) smaller babies. In the normal group (without gestational diabetes or hypertension, n = 503), maternal body weight before pregnancy and at term, maternal height, week of delivery, gender of the newborn, and parity were all significant, independent predictors of birthweight, together explaining 23% of the variability of neonatal weight. In addition, both fasting (p <0.006) and 2-h post-glucose (p = 0.03) maternal plasma glucose concentrations were positively associated with birthweight independent of the other physiological determinants, accounting, however, for only 10% of the explained variability. In a subgroup of 134 normal mothers with prepregnancy body mass index of less than 25 kg · m−2, in whom plasma insulin measurements were available, the insulin area-under-curve was inversely related to birthweight (p <0.02) after simultaneously adjusting for physiological factors and glucose area. When glucose and insulin measurements were combined in the I/G ratio (ratio of insulin to glucose area), this was still inversely related to birthweight. Furthermore, maternal insulinaemia was directly related to blood pressure levels (p <0.001) independently of body weight. We conclude that in normal pregnancy, whereas physiological factors account for most of the explainable variability of infant weight, the influence of the maternal metabolic milieu is dual, positive for glucose levels but negative for insulin concentrations. Maternal hyperinsulinaemia during pregnancy may be one trait linking low birthweight with predisposition to diabetes in adult life.