Maternal feed restriction may restrict fetal growth in part indirectly by impairing placental functional development. Such actions could be mediated by the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonstrated, less is known of the influence, if any, of that in the mother. This study aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restriction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal weight (r=0.65, P=0.008, n=17), volume of the maternal blood space (r=0.58, P=0.048, n=17), and surface density of syncytiotrophoblast (r=0.65, P=0.023, n=17), were positively correlated, and syncytiotrophoblast thickness was negatively correlated, with maternal plasma IGF-II concentration (r=-0.69, P=0.014, n=17). Late in gestation, fetal weight, placental weight and total exchange surface area in the placenta were each negatively correlated with maternal plasma IGFBP-2 concentration (all P<0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r=0.54, P=0.038, n=15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental weight (r=0.52, P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per cent (P=0.001) and this ratio was positively correlated with fetal weight (r=0.56, P=0.01, n=20), placental weight (r=0.59, P=0.006), placental diameter (r=0.621, P=0.003), placental volume (r=0.57, P=0.009), weight of trophoblast (r=0.51, P=0.037), weight of fetal capillaries (r=0.49, P=0.046), syncytiotrophoblast surface density (r=0.611, P=0.009) and negatively correlated with syncytiotrophoblast thickness (r=-0.55, P=0.021). Our results suggest that in mid-pregnancy, maternal circulating IGF-II promotes placental structural development, while later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term.