Whey protein concentrate and dried skim milk were each evaluated as the major protein source in milk replacer using four treatments (100% skim milk, 67% skim milk and 33% whey protein concentrate, 33% skim milk and 67% whey protein concentrate, and 100% whey protein concentrate). In the first trial, 64 calves were fed only milk replacer from birth to 6 wk of age. In the second trial, 61 calves were fed milk replacer and were allowed ad libitum intake of starter from birth to 6 wk of age. Calves were fed milk replacer at 10% of birth weight for the first 2 wk and at 12% of birth weight thereafter. In trial 1, average daily gains and feed efficiencies were significantly improved for calves that consumed the milk replacers containing 67 and 100% whey protein concentrate over those for calves that were fed the milk replacer containing 100% skim milk. No difference in growth or feed efficiency caused by treatment was detected in trial 2. Average daily gain in trial 2 was correlated with total starter intake. In trial 1, plasma glucose concentrations were correlated with growth rates and were highest for calves fed the milk replacer containing 67% whey protein concentrate. No differences were found for fecal scores or days scoured between trials. When only milk replacer was fed, higher proportions of whey protein concentrate improved calf performance, but, when starter was also provided, no effect of milk replacer was found.