AZT is a thymidine analogue useful in the treatment of AIDS. It has been demonstrated that this compound can possess a significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil (5FU) and methotrexate (MTX). Here we report a review of our data concerning the efficacy and tolerance of the combination AZT + MTX in HIV-related non Hodgkin's lymphomas (NHL). Twenty-nine patients were treated, at weekly intervals, with three (patient 1 to 10) or six (patient 11 to 29) consecutive courses of MTX 1g/m2 and increasing doses of oral AZT (2, 4 and 6g/m2) with leucovorin rescue. Of 26 evaluable patients, a total (complete + partial) response rate of 77% was obtained. The median complete response duration was 16.8 months. There was one therapy-related death due to septic shock. Grade III-IV neutropenia was observed after 19% of the courses, but was prevented by G-CSF administration in 82/119 courses. Grade III-IV anemia was observed after 9% of the courses. In conclusion, the combination AZT + MTX was effective and well tolerated in our series of HIV-related NHL patients.