Three hundred and sixty-nine patients with advanced ovarian adenocarcinoma were treated in a prospective randomized trial comparing combination versus sequential therapy with chlorambucil and cisplatin. Initial tumor response rates were similar but combination chemotherapy was associated with significantly prolonged time to first disease progression (median 28 weeks for chlorambucil and 42 weeks for combination chemotherapy). Secondline treatment with cisplatin in patients failing initial chlorambucil caused tumor response in 16.9%. Overall time to ultimate disease progression was similar between the treatment groups. The surgically documented complete response rate (second-look surgery at ≅12 months) and the survival was similar in the two treatment arms. Multivariate analysis of prognostic factors for survival in this trial showed that bulk of residual disease at time of starting therapy and the development of myelosuppression during therapy were the most important.