A hepatic human cell line (WRL-68 cells) was employed to investigate the uptake of the toxic heavy metal cadmium. Cd accumulation in WRL-68 cells is a time-, temperature- and concentration-dependent process. A rapid initial phase of uptake was followed by a second slower phase. The transport does not require energy and 55% of Cd transport occurs by temperature-insensitive processes, possibly by diffusion. The rest of Cd transport (45%) occurs by temperature-sensitive processes, probably ion channels and carriers, that involve interaction with sulfhydryl groups. The calcium channel blockers nifedipine and verapamil inhibit the uptake of cadmium, with an inhibition of 35% after 30 min incubation with 100 microM verapamil and 10 microM Cd. These data suggest that about one third of the Cd enters WRL-68 cells through the calcium channels. The toxic metals appear to use the transport pathways that exist for biologically essential metals. Our results in human hepatic cells are very similar to those reported in cultured rat hepatocytes. It appears that transport pathways available for Cd uptake are similar and independent of the species of hepatocyte origin. Moreover, the WRL-68 cell line seems to be an excellent in vitro model to study the mechanism of cell damage due to Cd.