This article reports the results of a randomized multicentric study comparing the efficacy of antithymocyte globulin (ATG) with cyclosporin-A (CsA) as first line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematological response and toxicity were compared. At 3 months, patients who had no or minimal response received the alternative therapy in order to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred and sixteen patients were analysed, 60 received CsA and 56 received ATG/PDN. The actuarial survival was 55% with a median follow-up time of 19 months. There was no significant difference in survival between the two groups. The main prognostic factor was the absolute neutrophil count (ANC) at entry: patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival when compared with patients with an ANC greater than 0.2 x 10(9)/L (P = 0.0001). At 3 months, 16% of patients had a complete or partial response and a cross-over treatment was given to 68 patients. At 12 months, 77 patients were alive, with a complete or partial response in 47 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had a sequential immunosuppression. The main complication was infection which was more often observed and was more often lethal during ATG and PDN. This study demonstrates that CsA is comparable to ATG for primary treatment of SAA, but it is less toxic with fewer infectious deaths.(ABSTRACT TRUNCATED AT 250 WORDS)