LLC-PK(1) kidney cells were cultured on filters, to investigate both apical and basolateral uptake and concomitant toxicity of cadmium. Two to four times as much (109)CdCl(2) was taken up through the basolateral side of the cell than through the apical side. Equally, toxicity was found to be consistently greater after basolateral exposure than after apical exposure. At a non-toxic concentration of 1 mum-CdCl(2), extracellular glutathione (GSH) (1 mm) and cysteine (1 mm) both lowered the rate and extent of uptake of Cd during the first 4 hr. This effect was more pronounced after basolateral than after apical exposure. A series of toxicity experiments was performed to investigate the time dependence of the protection by GSH and cysteine: after a 1-hr exposure to 200 mum both protected against toxicity; after 2 and 4 hr of exposure to 50 mum the protection of GSH was less pronounced than the effect of cysteine. As complex formation between Cd and GSH or cysteine is reversible, toxicity found in the presence of GSH and cysteine at higher concentrations or larger exposure times may very well be due to Cd ions released from the extracellular complex with these thiols. Thus, it seems that the toxicity is caused by the uptake of extracellularly available free ionic Cd.