Clearance of autoantibody-sensitized platelets through Fc gamma receptors on phagocytic cells is one of the main mechanisms of thrombocytopenia in idiopathic thrombocytopenic purpura (ITP). We examined the Fc gamma RIIA-131R/H and Fc gamma RIIIA-158V/F polymorphisms in 104 adult chronic ITP patients, and in 59 healthy control subjects using polymerase chain reaction-based allele-specific restriction analysis. The frequency of Fc gamma RIIA genotypes (131H/H, H/R, R/R) was not significantly different between patients and controls, and did not correlate with the responsiveness to treatment. In contrast, among Fc gamma RIIIA genotypes, frequency of 158F/F homotype was smaller in ITP (P < 0.05). Furthermore, in Fc gamma RIIIA-158V/V homotype, the complete remission (CR) rate with medication (treatment with corticosteroid or other immunosuppressive agents) was significantly higher (60%) than that in 158V/F (10%) or 158V/F plus 158F/F, (P < 0.01, P < 0.05). Conversely, the CR rate after splenectomy in 158F/F and 158V/F types (64.3% and 54.6%) was higher than in 158V/V (25%). Our results indicate that the polymorphism of Fc gamma RIIIA, but not Fc gamma RIIA, influences the response to treatment in ITP.