Post-transplant leukemic relapse remains the major problem following autologous bone marrow transplantation (ABMT). One possible approach to reducing the relapse rate is to intensify pre-transplant conditioning. Thiotepa (TTP) is an alkylating agent that has been used mainly in breast and ovarian cancer with 20-50% response rates. This report presents our results on 33 patients with acute leukemia (acute myeloblastic leukemia (AML) 27 patients, acute lymphoblastic leukemia (ALL) six patients) who underwent ABMT following conditioning with busulfan (BU), 4 mg/kg x 4 days (days -8 to -5), TTP 5 mg/kg x 2 days (days -4, -3) and cyclophosphamide (CY) 60 mg/kg x 2 days (days -2, -1). Of the 33 patients, 22 were males and 11 females, of median age 24 (1-55) years. Twenty-eight patients were transplanted in complete remission (AML 26; ALL 2) while 5 (AML 1; ALL 4) were in early relapse. Twenty-nine additional AML patients (15 females, 14 males) of median age 22 (2-48) years, who underwent ABMT following a standard BU-CY conditioning regimen (25 in complete remission and four in relapse) served as historical controls. There were no significant differences between the study and control groups with respect to patient age, sex, diagnosis, stage of disease, FAB classification, and prior chemotherapy, at ABMT. Overall survival, disease free survival (DFS), and relapse rate at 72 months were 33, 33 and 61%, respectively, for the study group, and 38, 34.5 and 52%, respectively, for the historical controls. Engraftment and transplant related toxicity also did not differ significantly in the two groups. In conclusion, TTP appears to have made no substantial improvement to the outcome of ABMT for acute leukemia.