Milk and other foods of animal origin have been shown to improve zinc absorption from phytate-rich diets. The ability of milk proteins and casein phosphopeptides (CPP), the latter formed during digestion of casein, to overcome the inhibitory effect of phytate on zinc and calcium absorption was investigated. Suckling rat pups were given aqueous phytate-containing solutions, oat diet, or soy formula alone or with milk proteins or CPP added. Diets labeled extrinsically with 65Zn and 47Ca were given by gastric intubation. Absorption was determined from measurement of radioisotope activity in intestine, organs, and carcass. Addition of CPP improved zinc and calcium absorption from aqueous phytate-containing solutions and from oat diet. The effect of CPP on calcium absorption from soy formula was less pronounced. The influence of CPP on zinc absorption from aqueous phytate-containing solutions was also examined using a human colon carcinoma-derived cell line, Caco-2. Binding + uptake of 65Zn was determined after incubation with these solutions. Phytate reduced zinc binding + uptake to 79% of the control value. Addition of 14 mumol of CPP/L increased zinc binding + uptake to 94%, whereas 36 and 72 mumol of CPP/L depressed zinc binding + uptake (75 and 39%). In conclusion, CPP improved zinc and calcium bioavailability from high phytate meals in the rat pup model. In the Caco-2 cell system, addition of 14 mumol of CPP/L showed a positive effect on zinc binding + uptake from phytate-containing solutions, whereas higher levels of CPP inhibited zinc binding + uptake.