The merits of N-unsubstituted indoles and cyclopent[b]indoles as DNA- directed reductive alkylating agents are described. These systems represent a departure from N-substituted and pyrrolo[1,2-a]-fused systems such as the mitomycins and mitosenes. The cyclopent[b]indole-based aziridinylquinone system, when bearing an acetate leaving group with or without an N-acetyl group, was cytotoxic and displayed significant in vivo activity against syngeneic tumor implants. These analogues were superior to the others studied in terms of both high specificity for the activating enzyme DT-diaphorase and high percent DNA alkylation. Alkylation by a quinone methide intermediate as well as by the aziridinyl group could lead to cross-linking. The possible metabolites of the most active indole species were prepared and found to retain cytotoxicity, suggesting that in vivo activity could be sustained. The indole systems in the present study display selectivity for melanoma and, depending on the substituents present, selectivity for non-small-cell lung, colon, renal, and prostate cancers. The cancer specificities observed are believed to pertain to differential substrate specificities for DT- diaphorase.