The chemotherapeutic potential of 1,10-phenanthroline (phen), and three of its transition metal complexes, namely [Cu(phen)2(mal)] Æ 2H2O, [Mn(phen)2(mal)] Æ 2H2O and [Ag2(phen)3(mal)] Æ 2H2O (malH2 = malonic acid) was determined using two human carcinoma cell lines (A-498 and Hep-G2). Phen and the three metal–phen complexes induced a concentration- dependent cytotoxic effect, with metal complexes demonstrating the greatest cytotoxic response. In comparative studies, IC50 values show cytotoxicity of between 3 and 18 times greater than that observed for the metal-based anti-cancer agent, cisplatin. All of the phen-based complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Also, the potential cancer chemotherapeutic application of these compounds was seen to be enhanced by results obtained from Ames tests, which showed all of the test agents and their phase I metabolites were non-mutagenic. Taken together, these results suggest that phen and the three metal–phen complexes may have a therapeutic role to play in the successful treatment and management of cancer.