The purpose of this study was to examine whether immune neutralization of muscle-produced insulin-like growth factor I (IGF-I) would prevent an appropriate anabolic response to refeeding in diabetic rats. Male Sprague-Dawley rats were made diabetic by partial pancreatectomy and were randomly assigned to be either control-fed, fasted, or fasted-refed (n = 7-8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles (P < 0.05). In both groups of rats, fasting lowered protein synthesis and increased proteolysis and subsequent refeeding returned both parameters to near basal values (P < 0.05). Neutralization of muscle IGF-I by the addition of IGF-I antibody to the incubation medium reduced protein synthesis an average of 22% for all groups (P < 0.05). However, rates of protein degradation were not affected. In nondiabetic rats, refeeding increased protein synthesis in both control and antibody-treated muscles (P < 0.05). Refeeding also increased protein synthesis in the control muscles from diabetic rats (P < 0.01). In contrast, muscles from diabetic rats that were incubated with anti-IGF-I did not increase protein synthesis in response to refeeding. These data suggest that immune neutralization of muscle IGF-I in hypoinsulinemic rats negated the ability of endogenous IGF-I to promote protein synthesis and thereby prevented an appropriate anabolic response.