Three ongoing, dose-escalation, phase I studies are evaluating the combination of raltitrexed with oxaliplatin or anthracyclines (with and without cisplatin). In study 1, patients with advanced solid tumours received 2.0-3.75 mg/m2 raltitrexed, followed 45 min later by 85-130 mg/m2 oxaliplatin (2-h infusion) every 3 weeks. In study 2, patients with advanced oesophageal or gastric adenocarcinoma received 2.0-3.0 mg/m2 raltitrexed with 50 mg/m2 intravenous (i.v.) epirubicin and 60 mg/m2 i.v. cisplatin every 3 weeks. In study 3, patients with advanced or metastatic gastric cancer received 2.5-3.5 mg/m2 raltitrexed followed by 30-60 mg/m2 i.v. doxorubicin every 3 weeks. In all studies, raltitrexed was given as a 15-min infusion. All the combinations evaluated were administered in convenient 3-weekly schedules and were generally well tolerated. Recommended doses for raltitrexed and oxaliplatin are the same in combination as for single-agent use, i.e. 3.0 mg/m2 raltitrexed and 130 mg/m2 oxaliplatin. The recommended dose of raltitrexed in combination with cisplatin and epirubicin is 2.5 mg/m2. No dose-limiting toxicities were observed during co-administration of the full single-agent doses of raltitrexed and doxorubicin (3.0 mg/m2 and 60 mg/m2, respectively); dose escalation is continuing. Preliminary efficacy results were encouraging, particularly for the combination of raltitrexed and oxaliplatin in patients with mesothelioma and advanced colorectal cancer. Preliminary data from these phase I studies suggest that the combination of raltitrexed with platinum-based agents and/or anthracyclines may represent useful regimens for the treatment of patients with advanced cancer. Further studies are required to identify the most effective combinations of raltitrexed with both established and new anticancer agents.