This paper deals with amino acid transport by renal and intestinal epithelium in vivo and contrasts the inhibitory effects of Hg, known for its ability to react with and inhibit function of cell membranes, with those of Cd2+. The metals were injected intravascularly as Hg-EDTA and Cd-mercaptoethanol, forms in which they are not sequestered by plasma protein but still able to react with the relatively high affinity binding sites on cell membranes, and consequently to be taken up into cells. Under these conditions, Hg rapidly depressed basolateral amino acid transport; in contrast, no overt effect of Cd was seen for at least 6 h. Similarly, and in absence of exogenous chelators, Hg in the intestinal lumen rapidly caused inhibition of cycloleucine absorption; this effect was not abolished by EDTA. An effect of Cd was seen only after a significant initiation delay. These results provide additional support for the previously proposed indirect action of Cd on epithelial solute transport in vivo, and for the suggested role of membrane binding sites in cellular metal uptake.