In this study, 20 micrograms.kg.-1.h-1 of recombinant human insulin-like growth factor I (IGF-I) was infused into normal healthy rats to examine the effects of IGF-I on glucose, protein, and energy metabolism in either overnight-fasting or parenteral-feeding states. The fed state was maintained by continuous intravenous feeding of a complete diet containing 838 kJ.kg-1.d-1, 2 g N.kg-1.d-1, and no fat. At each nutritional state, one-half of the animals received IGF-I infusion while the other half received saline as control. [14C-1]leucine and [3H-6]glucose were used to determine the effects of IGF-I on protein and glucose kinetics during fed and fasting states. The results showed that 1) infusion of IGF-I at this amount did not alter plasma glucose appearance and only marginally decreased plasma glucose concentrations in both nutritional states; 2) during fasting, IGF-I did not show anabolic effects on protein metabolism either at the whole-body level or in individual tissues. However, during feeding, IGF-I significantly stimulated exogenous nitrogen utilization by the whole body; and 3) IGF-I reduced the thermogenic effect of feeding. The results suggest that parenteral feeding may be an important variable in the response of protein anabolism to IGF-I in vivo.