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Clonogenic survival of HeLa, Chinese hamster and HaK cells after treatment with a range of cisplatin concentrations and exposure times was determined and cellular platinum concentrations were measured by PIXE. It was demonstrated that cisplatin cytotoxicity of the three cell lines varied considerably as a function of drug exposure dose. These differences are related to differential cellular drug uptake. Sensitivity to cisplatin has been shown to vary considerably between different cell lines (Bergerat et al., 1979; Fraval & Roberts, 1979). This may be related to the specific cytotoxic action of the drug which interacts with DNA by monofunctional binding to bases, chelation or bifunctional cross-linking to bases in the helix, either on the same strand or on opposite strands (Douple & Richmond, 1979). Relative cytotoxicity has been related to the amount of Pt bound to the DNA (Fraval & Roberts, 1979) or to interstrand cross-links (Zwelling et al., 1979). We have studied cisplatin action on HeLa, Chinese hamster and HaK cells, which display large differences in drug sensitivity to cisplatin. The aim of our study was to investigate the correlation between drug cytotoxicity and platinum uptake into the cells. Materials and methods Cell cultures Experiments were carried out with the following three cell lines: B 14 F 28 Chinese hamster cells, a lung fibroblast cell line with a mean cell cycle time of 12 h; HeLa S 3 cells and HaK cells (Syrian hamster kidney cells, Flow Laboratories) with an average cell cycle time of 20 h. Monolayer cultures of all cell lines were cultured in Eagle's minimum essential medium (MEM), supplemented with 10% calf serum, 0.01% neomycine, and 0.035% NAHCO3. They were kept in a humified CO2 incubator at pH 7.4 and 37°C (for further details, see Eichholtz-Wirth, 1980). Drug exposure Cis-diammine-dichloro-platinum (cisplatin), Platinex-solution, Bristol Myers, was used and appropriately diluted in Hank's solution immediately before use. Exponentially growing cells were subcultured and appropriately diluted. Four hours after seeding, cisplatin was added to the culture medium, and the cells were incubated for the appropriate exposure time. After exposure the medium was removed, the cells rinsed twice with Hank's solution and fresh culture medium added. Cell survival After incubation for 8 days (Chinese hamster cells) or 14 days (HeLa and HaK cells) the colonies were stained with methylene blue and those containing more than 50 cells were counted. The ratio of mean colony yields of treated to untreated cells-the surviving …