The independent effects of decreased food intake and diabetic hyperglycemia on serum GH, serum IGF-I and tissue IGF-I expression were examined in young streptozotocin-diabetic pigs. Each of three treatments (control, diabetic, and insulin-treated diabetic) were represented within three levels of regulated food intake (FI) provided as three meals per day equivalent to 100, 50, and 10% of the voluntary FI consumed by the untreated diabetics. Reduction of food intake was associated with decreased body weight gains, decreased serum IGF-I concentrations, and increased serum GH concentrations. Nutrient restriction also tended to decrease the relative abundance of IGF-I mRNA in liver and skeletal muscle. Diabetic pigs with hyperglycemia and hypoinsulinemia had higher serum concentrations of IGF-I than pair-fed controls, but exogenous insulin treatment of these diabetic pigs increased serum IGF-I even further and also tended to increase the relative abundance of IGF-I mRNA in liver and skeletal muscle. When the statistical effects of reduced FI were eliminated, neither the present form of diabetes nor exogenous insulin affected serum GH. In summary, diabetes-induced changes in IGF-I in these pigs depended primarily on the reduced level of food intake occurring in these hypoinsulinemic, hyperglycemic subjects.