Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1a,8,8a,8b))-8-((aminocarbonyl)oxy)methyl-4,8a-dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6-nitrosoazirino(2,3: 3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1, 11-diazetetracyclo(7.4.1.0^2,7,0^10,12)tetradeca-2-4-6-trien-6,9-diyl-diacetate (FK973). In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MTT)-based assay. Average IC₅₀ values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) =-0.788+(0.755×log(LD₅₀)), and relative antitumor activity, RAA (PPC/IC₅₀), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.