Our objective was to measure and compare apparent ileal digestibility, standard ileal digestibility, and true ileal digestibility of crude protein (CP) and amino acids (AA) in milk replacers (MR) containing all milk proteins (WPC) or with 50% of the CP provided by an enzyme-treated soybean meal (ESBM). A T-cannula was placed in the ileum of 9 Holstein calves (8 males and 1 freemartin female) at approximately 15 d of age. After 2 wk postsurgery, calves were randomly assigned to a 3 × 3 replicated Latin square with 5-d periods. Calves were fed twice daily at a rate of 2% (dry matter) of body weight (1.25 kg/d on average), reconstituted to 15% solids, and adjusted weekly. No starter was offered to minimize rumen development. Digesta samples were collected continuously during 12 h on d 4 and 5 of each period. Basal endogenous losses of AA and CP were estimated by feeding an N-free MR to each calf during 1 period. Total endogenous losses (basal + specific; END total ) were estimated by multivariate regression of the chi-squared distances between digesta and reference protein AA profiles. Ileal digesta pH with the ESBM diet was lower than that with the WPC diet. According to the piecewise nonlinear model of pH fluctuation, digesta pH during ESBM decreased more slowly after feeding and reached its nadir later than with the WPC diet. Diet did not affect average daily gain, but calves on the ESBM diet showed a bigger increment of withers height and lower mean fecal scores. The basal endogenous losses of AA and CP were 13.9 ± 1.1 and 22.4 ± 1.1 g/kg of dry matter intake, respectively. The estimated END total of AA and CP was higher with ESBM than with WPC. Accordingly, apparent ileal digestibility and standard ileal digest-ibility of most AA, CP, and total AA were lower or tended to be lower with ESBM. However, true ileal digestibility did not differ between diets for CP and all AA except Ala and Ile, which were greater with WPC, and Arg, which tended to be greater with ESBM. In agreement with the estimated differences in END total , we found that flows of digesta DNA and crude mucin were greater with ESBM. Substitution of 50% of the protein from whey with enzymatically treated soybean meal did not affect major nutrient digestibility or calf growth and even improved fecal consistency. Adjusting digestibilities of CP and AA in MR by endogenous protein losses is crucial when comparing bioavailability of alternative proteins and milk proteins.