We studied the toxicity and efficacy of adding in sequence 4 resistance modulators to combination chemotherapy and radiotherapy in the treatment of glioblastoma multiforme and poor prognosis anaplastic astrocytomas. Patients received cisplatin plus mitomycin-C concurrently with and following 60 Gy of radiotherapy administered over 6 weeks. Resistance modulators were added in sequence to chemotherapy in each cohort of 6 patients as follows: metronidazole + pentoxifylline (cohort 1); + dipyridamole (cohort 2), + beta carotene (cohort 3). Central nervous system toxicity (which ranged from drowsiness to seizures and loss of consciousness) was frequent. The incidence of gastrointestinal symptoms was substantial, but was usually mild to moderate in severity. Three of 11 patients evaluable for response achieved a partial remission with treatment. The median survival duration for all patients was 26 weeks from initial diagnosis. The study was terminated prematurely because of significant toxicity (in this study as well as in parallel concurrent studies of similar design in other tumor types) and apparent lack of benefit.