Ten patients with non-Hodgkin's lymphoma (NHL) and nine with Hodgkin's Disease (HD) received high-dose busulfan and etoposide (VP-16) prior to autologous bone marrow transplantation (ABMT). All patients with NHL and eight with HD had poor prognostic factors. Marrows from patients with NHL were purged with 4-hydroperoxy-cyclophosphamide. Busulfan (16 mg/kg body weight) was given orally over 4 days; VP-16 was administered as a single 4-h infusion. VP-16 was initiated at a dose of 60 mg/kg but reduced to 50 mg/kg after three of the first seven patients developed fatal toxicity. The 100-day regimen-related mortality was 21% (95% confidence interval 14%-46%). An absolute neutrophil count of 500/microliters was achieved at a median of 18 days in NHL and 23 days in HD. The median time to achieve a platelet count of 50,000/microliters was slower in HD (100 days) than in NHL (31 days) (p less than 0.05). Complete remissions were documented in four of nine evaluable patients with NHL and two of eight evaluable patients with HD. Actuarial survival at 18 months was 21% (95% confidence interval 3%-39%). The combination of high-dose VP-16 and busulfan as used in this study, although comparable to other regimens in efficacy, is associated with several toxicities.