We are trying to understand individual differences in susceptibility to chromate toxicity by comparing three different lymphoblastic cell lines derived from three different individuals. We have compared the uptake of CrO4(2-), the release of LDH from cells, the proliferation ability of the cells, and the DNA-protein crosslinks in these lymphoblastic cell lines exposed to chromate. We report here that one lymphoblastic cell line, GM0922B, appears to be considerably less sensitive than the other two cells lines to the cytotoxic effects of hexavalent chromium. The diminished sensitivity is almost twofold and can be accounted for by the decreased uptake of hexavalent chromium, which results in less lactate dehydrogenase release, and greater tolerance to chromate inhibition of cell proliferation and less DNA-protein crosslinking. This lower uptake of chromate combined with interindividual differences in extracellular Cr(VI) reducing capacity are probably the two most important determinants of genetic susceptibility to chromate toxicity.