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Mitozolomide and its decomposition product MCTIC were found to be more cytotoxic to BE colon carcinoma cells in vitro than to HT-29 cells, another colon carcinoma cell line. In addition mitozolomide and MCTIC induced DNA interstrand crosslinks in the BE but not the HT-29 cell line. BE cells are deficient in the repair of 06-methylguanine lesions and are designated Mer-, whereas, HT-29 cells are proficient in this repair process and are designated Mer+. Thus DNA interstrand crosslinking produced by mitozolomide and MCTIC appears to correlate with the Mer phenotype. Pretreatment of HT-29 cells (Mer+) with the DNA methylating agent MNNG allows mitozolomide or MCTIC to produce DNA interstrand crosslinks. HT-29 cells also become more sensititive to the cell killing of mitozolomide and MCTIC with MNNG pretreatment. Pretreatment of Mer-cells (BE) had little effect on either cell killing or DNA crosslinking levels induced by mitozolomide or MCTIC. DNA interstrand crosslinking induced by mitozolomide and MCTIC is probably a consequence of an initial alkylation at the 06-position of guanine followed by a delayed reaction with the opposite DNA strand. 8-carbamoyl-3-(2-chloroethyl)imidazol5, 1-dI-l, 2, 3, 5-tetrazin-4(3H)-one (mitozolomide) is a newly synthesised heterocyclic compound which demonstrates curative action against a wide variety of murine tumours (Hickman et al., 1984). Chemical studies have suggested that mitozolomide cleaves to