(NH3)2Pt(triacid) and (PPh3)2Pt(dehydrocholate)2 are novel bile acid-conjugated platinum complexes administered by oral route. The aims of the present study were to evaluate their in vitro cytotoxic activities on rat hepatoma cell line N1-S1, the in vivo antitumour effects in a syngeneic and orthotopic rat hepatoma model and the drug-related toxicities. Cisplatin, carboplatin and mitoxantrone were used as control drugs. In vitro experiments showed a concentration- and time-dependent antiproliferative activity of bile-conjugated platinum complexes. (NH3)2Pt(triacid) had similar effects on cell growth of cisplatin and carboplatin (e.g. at 48 h, IC50 0.7+/-0.05 microM vs. 0.63+/-0.28 microM and 1.1+/-0.3 microM, respectively; mean+/-S.D.). (NH3)2Pt(triacid) was able to inhibit tumour growth in a dose-dependent extent, reaching the maximum inhibitory effect at the 80 mg/kg dose (1.95+/-0.5 g vs. 13.85+/-3.9 g of control tumour weight). By contrast, despite the promising in vitro antiproliferative activity, (PPh3)2Pt(dehydrocholate)2 showed no significant in vivo antitumour effect. The toxicity profile of (NH3)2Pt(triacid) resulted favourable with minimal loss of weight and no gastrointestinal or neurological symptoms. Instead, (PPh3)2Pt(dehydrocholate)2 showed dose-dependent signs of severe weight loss and neurological alterations. In conclusion (NH3)2Pt(triacid) is a tolerable and active platinum derivative endowed by a preclinical antitumour activity by oral route.