We investigated whether tumor cell lysis by lymphokine-activated killer (LAK) cells was enhanced by treatment of the tumor cells with cisplatin (CDDP) in vitro. Tumor cells were treated with CDDP in vitro, and the cytotoxic activity for LAK cells was measured by 4-h 51Cr-release assay. The alterations of succinate dehydrogenase (SD) activity, and DNA,RNA synthesis of tumor cells were analysed. The susceptibility of CDDP-treated (2 micrograms/ml, 2h) Daudi and KATO-III cells to lysis by short term-cultured LAK cells was enhanced, as was the susceptibility of CDDP-treated (2 micrograms/ml, 12h) autologous tumor and Daudi cells to lysis by long term-cultured LAK cells. SD activity and DNA synthesis in tumor cells were impaired by 12-h treatment with 2 micrograms/ml of CDDP, whereas those were not altered by 2-h treatment with 2 micrograms/ml of CDDP. The enhancement of the susceptibility of CDDP-treated tumor cells to long term-cultured LAK cells was thus elucidated; it was shown to be due to alterations of the tumor cells with regard to their SD activity and DNA synthesis. It is suggested that the combined therapy with CDDP and LAK cells offers hope for increasing the response rate and the long-term survival of cancer patients.