Low IGF-I levels are found in patients with chronic liver disease, but it is not known whether these reductions in IGF-I are secondary to hepatic dysfunction or to malnutrition. To determine whether malnutrition associated with hepatic dysfunction causes the decrease in these levels, serum and liver IGF-I concentrations and liver IGF-I mRNA content were compared in three groups of Sprague-Dawley rats: 15 rats underwent bile duct obstruction; 10 rats were sham-operated and pair-fed with operated rats to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum. In addition, IGF-I peptide and mRNA were compared with food intake, crude nitrogen balance, total wt gain, tail length increase and leg muscle wt. All the parameters were lower in cholestatic and nutritionally deprived animals than in control animals (p < 0.001). There was no difference in serum and hepatic IGF-I and liver IGF-I mRNA values between the 10 cholestatic and pair-fed animals, despite lower crude nitrogen balance, tail length gains, and leg muscle wt in the bile duct-obstructed animals. These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-I levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. However, factors in addition to suboptimal nutrition and decreased IGF-I levels must also contribute to cholestasis-induced growth failure.