The influence that copper and zinc exert on each other's absorption was studied by using the isolated, vascularly perfused rat-intestine system. In the first series of experiments, rats were fed for 1 wk one of nine diets, with different copper and zinc concentrations representing low, adequate and high dietary metal intakes. Copper concentrations were 1, 6 and 36 mg/kg diet and zinc concentrations were 5, 30 and 180 mg/kg. The small intestine was perfused with M199 tissue culture medium containing 6 mg/L copper and 30 mg/L zinc. Neither metal was found to significantly alter the other's absorption. High dietary zinc increased metallothionein-bound copper but did not change the intracellular copper concentration. In the second series of experiments, the dietary copper and zinc concentrations were held at 6 mg/kg and 30 mg/kg, respectively, while the metal concentrations in the luminal perfusate were changed (from 1 to 36 mg/L and from 5 to 180 mg/L for copper and zinc, respectively). The higher copper concentrations in the perfusate increased zinc accumulation in mucosal cells and decreased the zinc transferred to the portal perfusate at the highest luminal zinc concentration. These data indicate that a competition and/or inhibition of a pathway for zinc out of the mucosal cell occurs at high luminal copper concentrations. High luminal zinc concentrations in the perfusate decreased the copper concentration in the mucosal cell cytosol and the amount transferred to the portal effluent. These results taken together indicate that a competition and/or inhibition of copper or zinc intake into intestinal cells occurs when the luminal concentration of the respective congener is very high.