Nutrient deficiency causes growth failure and decreases serum insulin-like growth factor-I (IGF-I) concentrations. Because IGFBPs modulate the concentrations and availability of IGFs in serum, IGF-binding proteins (IGFBPs) were measured along with IGF-I and IGF-II before and after 21 days of refeeding in 22 undernourished Bangladeshi children (2-4 yr of age) with shigellosis. The effects of a 150 Cal/kg.day diet with a normal protein (6%; n = 10) or high protein (15%; n = 12) content were studied. The results were compared with those of 25 age-matched healthy American children (controls). Body weight gain was better in patients receiving the high protein diet than in those receiving the normal protein diet. In both groups, initial IGF-I (32 +/- 6 and 24 +/- 7 ng/mL; mean +/- SD) and IGF-II (177 +/- 15, 174 +/- 45 ng/mL) concentrations were low compared to controls (100 +/- 12 and 542 +/- 29 ng/mL, respectively; P < 0.007). After refeeding, IGF-I increased to 160 +/- 26 ng/mL on the normal protein diet and to 322 +/- 41 ng/mL on the high protein diet, exceeding values in controls (P < 0.007). IGF-II increased more than 2-fold on each diet (P < 0.007), reaching control values. IGFBP-2 concentrations before refeeding were twice those in controls (750 +/- 200 vs. 317 +/- 33 ng/mL; P < 0.007) and normalized after refeeding in the high protein group (288 +/- 32 ng/mL; P = NS), but remained elevated in the normal protein group (526 +/- 77 ng/mL; P < 0.007). IGFBP-3 levels before refeeding were low and returned to normal on each diet. IGFBP-3 proteolytic activity in serum was initially increased and declined on the high protein diet. In conclusion, protein content in the refeeding diet differentially affects IGFs and IGFBPs in young undernourished children with infection. IGF-I and IGFBP-2 seem to be particularly sensitive to dietary protein alterations. We speculate that an increase in IGF-I concentrations, normalization of IGFBP levels, and a decrease in IGFBP-3 proteolytic activity in serum may all be involved in the improved recovery and catch-up growth observed with the high protein diet.