Human lung cancer sublines resistant t o cisplatin (CDDP) have been developed by continuously exposing cells to gradually increasing doses of CDDP and use of the limiting dilution technique. The cell lines used were PC-7, PC-9 and PC-14 (pulmonary adenocarcinoma) and H69 and N23 I (small-cell lung cancer). The resistant phenotype of the resistant sublines was stable for more than 2 months in the absence of drug. PC-7/1.2 (i.e., PC-7 cells growing stably in medium containing 1.2 pg/ml of CDDP), PC-9/0.5, PC-14/1.5, H69/0.4, and N231/ 0.2 have been developed, which are 22.9, 7.1, 3. I, 25.6, and 8.4 times more resistant t o CDDP than the respective parent cell line in terms of ICs0 in the soft agar colony assay with continuous drug exposure. Cloning efficiency decreased significantly in N231/0.2. The doubling times increased significantly in most of the resistant sublines. Cellular D N A contents increased in all resistant sublines, but statistical significance was observed only in H6910.4 @<0.05). Cells of the resistant sublines of PC-7, PC-9, PC-14 and H69 were larger than cells of the parent lines, but the differences were not significant. The growth morphologies of all resistant sublines in the drug-free medium were similar t o those of parent cell lines. All resistant sublines tested were significantly cross-resistant t o carboplatin. The patterns of cross-resistance, cross-sensitivity and collateral sensitivity t o adriamycin, mitomycin-C, 5-fluorouracil, vindesine, etoposide, aclacinomycin and vincristine were different in each resistant subline. Verapamil (3.3 pg/ml) showed little modifying effect on CDDP resistance in 5 CDDP-resistant sublines tested except N231/0.2 (Modification Index: 0.49). Cyclosporin A (5.0 pg/ml) modified CDDP resistance in CDDPresistant small-cell lung cancer sublines (H69/0.4 and N23 110.2) (Modification Index: 0.45 and 0.07, respectively), while in CDDP-resistant NSCLC sublines (PC=I/I .O and PC-9/0.5), cyclosporin A reduced the sensitivity t o CDDP. c