Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy was performed in five cases of recurrent glioblastoma multiforme. The mean age of cases, three males and two females, was 60 +/- 5 years old. All of the tumors were confirmed pathologically as glioblastoma multiforme and recurred after the initial treatments (surgery and irradiation). A total number of 1 x 10(9) vector producer cells (VPCs), which produce retroviral vectors containing the HSV-TK gene, was inoculated into the tumor-bed spaces after removal of the recurrent tumors. From the following 14th day to the 27th day, GCV was transfused 5 mg/kg i.v. twice a day. The effect of the HSV-TK/GCV gene therapy was evaluated by the Karnofsky performance scale and MRI findings sequentially, before the therapy and in the 1st, 2nd, 4th and 6th month after the VPCs inoculation. During the follow-up period of 12 months, two cases died (survival period; 8.4 and 9.9 months), whereas the other three are still alive for over 12 months (1-year survival; 60%). Karnofsky performance scale showed the maximum at the 2nd and 4th month in all cases; the mean performance rating of living cases was 80% and that of dead cases was 70%. MRI revealed progression in none of the cases until the 2nd month. These results obtained in five cases suggest that the HSV-TK/GCV gene therapy may promise a feasible approach against glioblastoma multiforme.