Novel ruthenium(II) organo-metallic compounds are active in ovarian cancer models [Aird RE, Cummings J, Ritchie AA, Muir M, Morris RE, Chen H, et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br J Cancer 2002;86(10):1652–7]. [(η 6 -C 6 H 5 C 6 H 5 )Ru(en)Cl] + (as a PF 6 salt, where en=ethylenediamine (RM175)) has been evaluated in a 13-cell line panel. Particular sensitivity (∼10-fold lower than mean IC 50 ) was noted in breast cancer and non-small cell lung cancer cell lines. In addition, IC 50 in the A549 was 2μM and RM175 (25mgkg −1 , days 1 and 5, i.p.) caused a significant (p=0.004) growth delay in a xenograft model. HC11 [(η 6 -tetrahydroanthracene)Ru(en)Cl]PF 6 was more potent in the A549 cell line (IC 50 0.5μM). HC11 (25mgkg −1 , days 1, 8 and 15, i.p.) was also active in vivo. Following RM175 25mgkg −1 , days 1 and 5, and 15mgkg −1 , days 1–5, HC11 25 and 40mgkg −1 , day 1, elevated alanine transaminase levels were detected, suggesting hepatotoxicity. No changes were observed in kidney or haematological parameters. In liver sections, multi-focal hepatic necrosis was seen, becoming confluent at high doses of HC11. In vitro studies confirmed that HC11 was more toxic than RM175 to fresh human hepatocytes and equitoxic to mithramycin. Liver toxicity may be related to the arene ligand and modification may reduce the potential for hepatic toxicity, while maintaining the anti-tumour activity seen.