The toxicity of a new chemotherapeutic regimen for CNS tumors using eight anticancer agents administered in a 12-hour period was evaluated in 34 children with newly diagnosed and recurrent tumors treated at the Children's Hospital and Medical Center in Seattle. The chemotherapy included methylprednisolone, vincristine, lomustine (CCNU), procarbazine, hydroxyurea, cisplatin (CDDP), and either cyclophosphamide or imidazole carboximide (DTIC). The first five patients additionally received high-dose methotrexate (HDMTX), but because of excessive toxicity this was replaced by cytarabine. Of 125 courses administered without HDMTX, red cell transfusions were required in 15% of the courses and platelet transfusions were required in 8%. Hospitalization for empiric treatment of fever associated with neutropenia occurred in 6% of courses. Three episodes of documented sepsis occurred. Virtually all hematologic toxicity occurred in patients with recurrent disease. Renal toxicity occurred in 14% of patient courses. One patient died of renal failure and sepsis following therapy. Neurologic and hepatic complications were infrequent. High-frequency hearing loss above the voice range was common, but clinically significant hearing loss occurred in only three patients. Severe nausea and vomiting were infrequent. Overall, the toxicity of "eight in one" chemotherapy in newly diagnosed patients was minimal; toxicity was greater in patients with recurrent disease.