The authors present their experience with salvage chemotherapy for oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chemotherapy, all seven (100%) responding to PCV. Administration of PCV was effective after regimens of carmustine and CCNU but was ineffective after prior administration of PCV. When PCV had been given any time previously, only four (19%) of 21 patients responded to salvage chemotherapy; however, four (40%) of 10 patients who received etoposide (VP-16)/cisplatin (CDDP) responded. Despite the small number of patients, two noteworthy trends emerge from these data: first, PCV is a highly effective salvage treatment when used at tumor recurrence following non-PCV chemotherapy regimens, and second, the synergistic combination of VP-16 and CDDP may exert substantial anti-oligodendroglioma activity, and it warrants further evaluation.