Nineteen patients with malignant lymphomas were treated with 52 courses of high dose methotrexate with leucovorin rescue (HDMTX-LCV): 17 non-Hodgkin's lymphoma (11 nodal primary, and 6 Waldeyer's ring), 1 Hodgkin's disease, and 1 Burkitt's lymphoma; 10 No prior chemotherapy, 9 prior chemotherapy; Median age 50 years (18-67); Sex M 13:F 6. MTX was given according to Frei III et al's regimen(1975). In brief, alkalinization of the urine was achieved by administration of NaHCO3 both by oral and by intravenous route. Hydration with at least 3 liters of fluid per day was maintained throughout each course. MTX was administered as a six-hour infusion at an initial dose of 0.5-1.0 g/m2 with gradual escalation to 3-5 g/m2. Thirty minutes before the infusion of MTX, 1.4 mg/m2 of vincristine (VCR) (maximum dose 2 mg) was given intravenously in each course. MTX levels were not monitored. The overall response rate was 63% with 7 partial responses and 5 complete responses. Five of 10 previously untreated patients and 7 of 9 patients with prior chemotherapy achieved an objective response. Our excellent result may be contributed in part by VCR. Although, in general, during this study HDMTX-LCV was well-tolerated, a 67 year-old male had severe and unpredictable toxicity which resulted in shock condition, leukopenia and thrombocytopenia. Accordingly, we feel that HDMTX-LCV is dangerous without monitoring plasma MTX level. In other side effects, peripheral neuropathy and constipation possibly due to VCR occurred especially in elderly patients.