Toxic metals appear to use the transport pathways that exist for biologically essential metals. Calcium uptake in cells occurs through specific membrane channels. Since cadmium inhibits calcium uptake, this study was carried on to elucidate the mechanism of Cd interference with calcium transport using the fetal hepatic cell line WRL-68 as an in vitro model. Ca accumulation by WRL-68 cells presented an initial rapid phase, followed by a sustained phase of slower accumulation over a 60 min period. A concentration of 50 microM CdCl2 produced 39% inhibition of the uptake of CaCl2 (100 microM), while 100 microM nifedipine or verapamil decreased Ca accumulation by 35 and 63%, respectively. All Cd concentrations tested produced significant decrease in Ca uptake in a concentration-dependent manner at 1 min and thereafter, although with 10 microM CdCl2 no significant difference was found after 30 min of incubation. From the Lineweaver-Burk plot, we found that Cd exerted a competitive inhibition on Ca uptake, since there was no significant effect on the Vmax but an increased K(m). A second order rate constant of Cd inactivation of 0.061 mM-1.s-1 was determined from the course of Ca uptake during Cd inhibition. SH groups seemed to play an essential role in Ca inhibition uptake by Cd because the inhibition of Ca accumulation by 50 microM Cd was practically reversed after the addition of dithiothreitol.