The hypothesis was tested that Cd absorption from the intestinal lumen is mediated by cellular transport systems. Cd is readily extracted from glucose-saline during perfusion of jejunal segments in the living rat. Over periods as long as 40 minutes, essentially all extracted Cd is recovered in the wall of the intestine. Cd uptake by the tissue obeys saturation kinetics with Km values of the order of 0.1 mM, and Vmax approximately 0.01 umol/g/min. Although washing after exposure to 109Cd removes only little radioactivity from the tissue, it reverses at least partly the saturating effects of higher Cd concentrations. Unidirectional flux of Cd into the tissue is inhibited by 10 mM Ca; no effect on backflux of Cd is seen. In contrast, Zn and EDTA both accelerate washout of Cd. The Ca content of skimmed milk fully accounts for the depressing effect of dried milk on Cd uptake. These results point to the presence in mucosal cell membranes of a saturable process responsible for Cd uptake and sensitive to inhibition by certain solutes in the lumen.