We performed a nutritional trial to assess the variations of circulating insulin-like growth factor-I (IGF-I) in chronic renal failure (CRF). Eight patients suffering from mild renal failure (SCr = 374 +/- 52 mumol/l) were prescribed a standard diet for 1 month followed by 1 month of protein restriction. Mean protein intake was 0.77 and 0.46 g/kg BW/day, mean caloric intake 25 and 24.7 kcal/kg BW/day for the first and the second month, respectively. After each period of diet, nitrogen balances were negative (-1.2 +/- 1.6 and -1.6 +/- 0.9 g/N/day). Despite these low-caloric conditions, mean serum IGF-I level was at the upper level of normal (358 +/- 136 ng/ml) after 1 month of standard protein intake, and statistically reduced (289 +/- 122 ng/ml, p < 0.002) by the low-protein diet. No correlation was observed between serum IGF-I levels and protein, caloric intake, and nitrogen balances for the two periods. Estimation of the IGF-I binding by the ratio of extracted to nonextracted IGF-I value suggested abnormal binding in CRF. This binding was modified by reduced protein intake. In conclusion, larger studies are needed in CRF to assess the significance of IGF-I variations and the IGF-I binding proteins which modulate the bioactivity of this growth factor.