The hypothesis was that calves fed high-fat milk replacers (MR) would have reduced starter intake, digestibility, and average daily gain (ADG). Forty-eight Holstein calves (initially 42.4 +/- 1.5 kg of body weight, 2 to 3 d of age; 12 calves/treatment) were fed 0.66 kg dry matter (DM) of MR per calf daily that contained 14, 17, 20, or 23% fat. This MR had crude protein (CP) to metabolizable energy (ME) ratios ranging from 51.6 to 56.7 g of CP/Mcal of ME, which were above and below a previously determined optimum. Calves were weaned at 28 d; postweaning measurements were continued to d 56. A 20% CP starter and water were fed ad libitum all 56 d of the trial. Measurements of digestion were made using chromic oxide as a marker in the MR and starter from fecal samples collected on d 19 to 23 from 4 calves/treatment. Selected serum constituents were measured on d 21. Calves were housed individually in pens bedded with straw within a naturally ventilated barn with no added heat. The average barn temperature was 2 degrees C. Data were analyzed as a completely randomized design using polynomial contrasts to separate differences in the means. Preweaning apparent digestibility of DM, organic matter, fat, nonfiber carbohydrates, Ca, and P and serum amylase concentration were linearly reduced as fat increased from 14 to 23%. Preweaning starter intake responded quadratically to fat, being lowest at 14 and 23% fat. A reduction in digestibility and starter intake contributed to less ADG at the higher fat concentrations in the MR. A 27% CP, 17% fat MR with 55 g of CP/Mcal of ME maximized preweaning ADG when fat concentration was varied to obtain various CP to ME ratios in the MR. Additionally, a 27% CP, 20% fat MR with 53 g of CP/Mcal of ME supported overall ADG similar to calves fed the 17% fat MR but preweaning digestion measurements and serum amylase concentrations were less than in calves fed the 17% fat MR.