BACKGROUND/OBJECTIVES: Milk increases both fasting insulin and insulin-like growth factor 1 (IGF-1), and thereby growth, in healthy prepubertal boys. It is, however, unknown which components in milk are responsible for milk's growth-stimulating effect. SUBJECTS/METHODS: To get closer to the identification of which components in milk that stimulate growth, we have performed an intervention study with 57 eight-year-old boys in which we examined the effects of the two major milk protein fractions, whey and casein, and milk minerals (Ca and P) in a 2 x 2 factorial design on IGFs and glucose-insulin metabolism. The amounts of whey and casein were identical to the content in 1.5 l skim milk. The amounts of Ca and P were similar to 1.5 l skim milk in the high-mineral drinks, whereas the amounts of Ca and P were reduced in the low-mineral drinks. RESULTS: There were no interactions between milk mineral groups (high, low) and milk protein groups (whey, casein). Serum IGF-1 increased by 15% (P<0.0001), whereas there was no change in fasting insulin (P=0.36) in the casein group. In the whey group, fasting insulin increased by 21% (P=0.006), with no change in IGF-1 (P=0.27). There were no independent effects of a high milk mineral intake on IGF-1 and insulin. CONCLUSIONS: The main milk protein fractions exhibit important but different growth-promoting effects by increasing either fasting insulin (whey) or IGF-1 (casein) levels.