The effects of different protein intakes on wt gain, insulin secretion, and plasma concentrations of amino acids have been evaluated in a prospective study involving 30 normal term infants. The infants were studied from 4.0 to 6.0 mo of age. Ten infants were breast-fed (BF), the others were randomly divided into two groups of 10 infants. One group was fed a formula containing 1.3 g protein/100 mL (F 1.3), the other a formula with 1.8 g protein/100 mL (F 1.8). The formulas were isocaloric (72 kcal/100 mL), and the fat concentrations were 3.5 g/100 mL (F 1.3) and 3.2 g/100 mL (F 1.8). All infants received the same supplementary foods. The urinary C-peptide excretion in the infants fed the F 1.8-formula was 4.4 +/- 2.1 nmol/mmol creatinine or 19.4 +/- 12.9 nmol/m2, significantly higher than that in the infants fed the F 1.3-formula (2.6 +/- 1.5 and 7.9 +/- 5.1) or the BF infants (1.7 +/- 1.4 and 6.3 +/- 6.0). Gain in wt was 18.0 +/- 4.3, 19.9 +/- 3.9, 22.8 +/- 1.6 g/kg/wk and corresponded to protein intakes of 1.3 +/- 0.2, 1.9 +/- 0.3, and 2.6 +/- 0.2 g/kg/d, in the BF, F 1.3, and F 1.8 groups, respectively. Gain in length was 6.7 +/- 1.8 (BF-group), 6.2 +/- 2.5 (F 1.3-group), and 7.6 +/- 2.2 (F 1.8-group) mm/m/wk. Wt gain correlated with urinary C-peptide excretion at 6.0 mo (r = 0.51, p less than 0.01) and with protein intake (r = 0.43, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)