The current study was performed to evaluate the efficacy and toxicity of a chemotherapy treatment using melphalan administered over a 24-h period with individual adapted dosing in advanced ovarian cancer. Melphalan was infused intravenously with an automatic infusion pump over a 24-h period. The schedule was repeated every 28 days for a maximum of 6 cycles. The initial administered dose was 25 mg/m(2). Drug adjustment was then made using a population approach, with the aim of constraining the overall area under the plasma concentration-time curve within 2.0-2.5 mg . h/l. A total of 96 courses of chemotherapy was administered. The toxicity profile did not differ greatly from that reported after a 1-h infusion and was acceptable in such a heavily pretreated patient population. Twenty-five patients were assessable for response and survival. Four (16%) partial responses were observed, which lasted 9, 10, 13 and 37 months, respectively. Three patients experienced stable disease during 8, 14 and 22 months, respectively. The 1- and 2-year survival rates were 18% and 6%, respectively. At the time of analysis, two patients remained alive with progressive disease at 22 and 37 months, respectively. In conclusion, melphalan administered over a 24-h period in platinum- and taxane-resistant ovarian cancer patients appeared to provide some clinical benefits with manageable toxicity. Based on these results, future studies comparing melphalan administered over a 24-h period and oral melphalan administrations will be scheduled.