✓ Twelve patients were admitted to a Phase II study on the treatment of recurrent glioblastoma multiforme with interferon-β (IFN-β). All patients had previously undergone craniotomy and received a standard course of radiation therapy. Recurrence was inferred from enlargement of the lesion on computerized tomography (CT) scanning and in each case was confirmed by CT-guided stereotaxic biopsy. Treatment consisted of combined intravenous (10 × 106 IU/day) and intratumoral (1 × 106 IU every other day) administration of IFN-β over three 10-day cycles. This regimen was well tolerated, with toxicity requiring temporary dose modifications in five patients. As judged from data from historical cases, however, the patients admitted to this study demonstrated no clear improvement in mean survival time. The findings of this study also emphasize the importance of distinguishing between radiation necrosis and tumor recurrence.