The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.