This trial is based on the strategy of reversing O-6-methylguanine-DNA methyltransferase (MGMT)-mediated nimustine resistance by depleting MGMT activity with streptozotocin (STZ) pretreatment. Eight patients with recurrent malignant gloiomas refractory to previous nimustine chemotherapy were entered in this study. Patients received STZ (2g/m(2)) followed one hour with nimustine (2-3 mg/Kg) via the ipsilateral carotid artery. After 1-2 cycles of therapy, 3 patients responded, 4 stabilized, and 1 failed. Toxic effects were generally tolerated. The preliminary results indicated that nimustine-resistant tumor cells in vivo could also be sensitized by modulation of MGMT activity.