Before the advent of the operating microscope and the carbon dioxide laser, reoperations were performed in less than 5% of patients with malignant astrocytoma. Between 1978 and 1981, a consecutive series of 74 adult patients were prospectively treated with operation, radiation, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy. After the failure of primary therapy, all patients eligible for further treatment were offered reoperation with the microscope and/or laser before treatment with Phase I agents (microwave hyperthermia, dimethyl sulfoxide (DMSO)-Adriamycin, DMSO-Cytoxan, or azaridinylbenzoquinone (AZQ)). Forty-six per cent of the patients were referred from outside institutions for intensive treatment. In 36 months, 40 patients received second operations directed at their tumor and had a median calculated survival from the time of reoperation of 37 weeks. The length of survival after the second operation was independent of patient age, performance status, tumor grade, and interoperative interval. Sixty-five per cent of patients under 40 and 48% of patients over 40 underwent reoperation with minimal morbidity and no deaths. The single most important prognostic factor for survival in both reoperated and single-operated patients was age. Tumor grade had no influence on survival in the series as a whole, in patients under 40 years of age, or in reoperated patients. The calculated median survival for the entire series was 15 months, with a predicted 2-year survival rate of 0.25. These figures include all patients treated without exclusion for incomplete radiotherapy or chemotherapy. It is concluded that reoperation for malignant astrocytoma is safe, feasible, and of potential benefit in combination with other therapies. The routine use of reoperation to “set up” other treatment modalities deserves further study.