In the hope of eventually using replication-competent, neurovirulence-attentuated Herpes simplex type 1 virus in the treatment of brain tumors in humans, we analyzed the effect of such a mutant in human malignant meningioma transplanted into nude mice. Two models were used, one subcutaneous, the other intracranial subdural; nine or ten animals were used in each group. A 1 mm tumor mass was implanted. In the subcutaneous model, after 7 or 12 days, the tumors had reached size of 6 or 10 mm, respectively. At this time either saline or the attenuated, lac Z HSV-1 mutant G207 (5 × 106 PFU/50 μ1) were injected into the tumor; for the 10 mm tumors, the identical dose and 5 × 106 PFU/50 μl were given. Animals were sacrificed up to 28 days later. The ratio of tumor volume between untreated and treated groups was compared by the t-test. For all three treatment groups, tumor growth was markedly inhibited (p < 0.0001). In the intracranial model, either saline or G207 at a dose of 2 × 106 PFU/2 μl was injected into the tumor implant on day 7, with 9 animals in each group. By day 31, all animals in the control group had died; in the treated group, three were still alive at day 66; a significant difference in survival was found (Wilcoxon test, p < 0.01).