ABSTRACT.In this study, the experimental model of Wigglesworth was used to limit the maternal blood supply to the rat fetus and induce intrauterine growth retardation. The associated changes in plasma somatomedin activity, insulin, glucose, and cartilage metabolic activity are reported. The mean body weight ( ± SEM) of 108 fetuses in ligated uterine horns was significantly lower than that of 146 control fetuses (ligated, 2820 ± 50 mg; control, 3180 ± 50 mg;p< 0.001), as was mean nose-tail tip length (ligated, 55.6 ± 0.4 mm; control, 59.4 ± 0.3 mm;p< 0.001) and mean liver weight (ligated, 222 ± 5 mg; control, 274 ± 5 mg;p< 0.001). The uptake of [35S]sulfate by fetal costal cartilage in basal culture medium was significantly lower in growth-retarded fetuses than in controls. Plasma somatomedin activity measured by fetal rat cartilage bioas-say was significantly lower in growth-retarded than in control fetuses (p< 0.001). The growth-retarded fetuses were relatively hypoinsulinemic and hypoglycemic compared to control animals. These studies suggest that nutrient supply may become a limiting factor in the release of insulin and the circulating levels of somatomedin activity in the rat fetus, and hence in its growth.