Cd2+, Cu2+ and Hg2+ (0.5 mM) inhibit the absorption of D-galactose (1 mM) across rat jejunum in vivo. The inhibition increases by 3-5 min previous exposure of the mucosa to the heavy metals, and is appreciably reversed by washing the intestinal lumen with 10 mM EDTA, and in higher proportion with 10 mM dithioerythritol. The metals do not affect the passive absorption of galactose (sugar transport blocked by 0.5 mM phlorizin), or that of L-sorbose. In vitro accumulation of D-galactose by jejunum rings is also inhibited by Cd and Cu. This inhibition is reversed by washing more readily than in vivo. The metals do not affect sugar entry into the tissues in the presence of 0.5 mM phlorizin. The inhibition of the transport component follows a non-competitive kinetics. Cd and Cu inhibit also the L-phenylalanine accumulation by the jejunum rings, but they do not modify the passive entry (in the presence of 40 mM methionine) or that in the absence of Na+. Heavy metals appear to inhibit sugar and amino acid intestinal absorption by their binding to proteins (prevailing to thiol groups) of the luminal membrane of enterocytes, which pertain or are functionally related to the corresponding Na(+)-substrate cotransport system.