Differential scanning calorimetry (DSC) was used to study the interaction of platinum complexes with the linearized plasmid pJL3-TB5 DNA. An effective antitumor drug, cis-dichlorodiammineplatinum(II) (cis-DDP), caused the positions of DSC peaks to shift to a lower temperature range, showing that the heat stability of DNA decreases due to the adduct formed by the cis-DDP; the antitumor-inactive geometrical isomer trans dichlorodiammineplatinum(II) (trans-DDP) caused a larger variation in the melting profile than cis-DDP did. With another antitumor platinum complex, l,2-cyclohexanediamine(dach)platinum chloride (PtC12(dach)), a complex with higher antitumor activity, the effect on the melting profile was smaller than that of others with less antitumor activity. These results show that the antitumor activity of platinum complexes is inversely proportional to their ability to disrupt DNA structure.The transition of double-stranded DNA to single-stranded DNA occurs when temperature rises. This melting process takes place blockwise and cooperatively along the double-stranded DNA molecule (1,6,(23)(24)(25). Recently, Maeda et al. (9,10) showed that DSC can detect the fine structure of the melting of plasmid DNA. The DSC curve agrees well with the theoretical melting curve for the DNA, so it is possible to assign the DSC peaks to the particular regions in the deoxyribonucleotide sequence. This has made it possible to study the interaction of drugs with DNA and to know their effects on the gene function. Antitumor drug cis-DDP is generally considered to elicit its antitumor activity as a result of interaction with . Recent studies have shown that the major adduct formed in DNA by cis-DDP is an intrastrand crosslink between two adjacent purines on one strand of DNA (3,18, 21). A trans-isomer of cis-DDP does not form this major adduct,