Methylglyoxal bis(guanylhydrazone) (MGBG; NSC 32946) is currently being reevaluated for its clinical antineoplastic activity against hematological and solid tumors. MGBG (100-200 mg/m2) was administered by slow infusion over 3 h to 6 patients during surgical resection of intracerebral tumors. Excised tumor tissue and plasma were assayed for MGBG by high-pressure liquid chromatography. In all cases, MGBG penetrated rapidly into brain tumor tissue. Viable tumor tissue contained greater concentrations of MBGB than did necrotic tumor tissue. In 2 patients with glioblastoma multiforme, MBGB concentrations in brain tumor tissue were 5- to 19-fold higher than concurrent plasma samples. MGBG did not penetrate well into the CSF of 2 patients with Ommaya reservoirs given i.v. MGBG (200 mg/m2). The highest MGBG concentration in CSF reached only 22% of the concurrent plasma levels. MGBG may be a useful agent in the treatment of intracerebral tumors but may not be effective against meningeal leukemia and meningeal carcinomatosis.