OBJECTIVE To assay the factors that may predict the response to immunosuppressive therapy (IST) in severe aplastic anemia patients. METHODS The blood samples were collected from 37 patients diagnosed as severe aplastic anemia in West China Hospital of Sichuan University and West China Second Hospital of Sichuan University during February, 2006 to March, 2007. Twenty healthy blood donors were used as normal control. The plasma levels of IFN-gamma and IL-2 were measured by enzyme linked immunosorbent assay, and the gene phenotype of HLA-DRB1 * 15 and HLA-DRB1 * 1501 was analyzed by polymerase chain reaction with sequence specific primer. The expressions of CD55 and CD59 on the cellular membrane of red blood cell and white blood cells also were measured. RESULTS The response rate in the patients who had higher IL-2 level before IST was significantly better than that in the patients with lower IL-2 level (66.7% vs 28.6%, P<0.05), while similar result was observed to IFN-gamma (73.7% vs 25.0%, P<0.05). The response rate in the patients with positive HLA-DRB1 * 15 was higher than that in those negative patients (62.5% vs 44.4%, P>0.05), but there was no different found in different HLA-DRB1 * 1501 phenotypes (50% vs 50%, P>0.05). The response rates in the patients with deficient CD55 and CD59 expression were higher than those expressed CD55 and CD59 normally (80.0% vs 40.0%, P>0.05); the response rate of patients younger than 40 years was higher than those older than 40 years (60.0% vs 14.3%, P<0.05); the response rate in female patients was higher than male patients (62.5% vs 42.9%, P<0.05). CONCLUSIONS The concentration of IL-2, IFN-gamma before IST, and age can be used as the predicting factors to immunosuppressive therapy, while the predicting value of HLA-DRB1 * 15, HLA- DRB1 * 1501 and CD55, CD59 to the response of IST still remain unclear.