BACKGROUND We have tested the hypothesis that insulin-like growth factor-I (IGF-I) or insulin can prevent the protein catabolic effects of tumor necrosis factor (TNF). METHODS After a 2-hour basal period TNF was infused (prime, 2.5 micrograms.kg-1; constant, 31.25 ng.kg-1.min-1) for 4 hours into conscious dogs to create the catabolic state. After 2 hours of TNF infusion either recombinant human IGF-I (n = 5) or recombinant human insulin (n = 5) was infused for an additional 2 hours. A third group (n = 5) received TNF alone for 4 hours. RESULTS TNF infusion caused an increase in both glucose production, reflected by [6,6-d2]glucose tracer data, and net protein catabolism, reflected by both [1-13C]leucine and [15N2]urea tracer methods. IGF-I and insulin both significantly reduced the rates of appearance of leucine and leucine oxidation to a similar extent, resulting in the significant decrease in net protein catabolism. CONCLUSIONS IGF-I and insulin can ameliorate the catabolic effects of TNF on protein and glucose metabolism equally effectively, although more IGF-I is required on a molar basis.