A polymorphism of the gene for Fc gamma RIIA, arginine (R) or histidine (H) at position 131, alters the ability of the receptor to bind certain IgG subclasses. Identification of the Fc gamma RIIA-H/R 131 genotype has assumed increasing importance in disorders of host defense, immunohematologic diseases and systemic autoimmune disorders. We report a new method for determination of this genotype in which an allele-specific restriction enzyme site is introduced into an Fc gamma RIIA PCR product from genomic DNA, and polymorphism assignment is determined by restriction enzyme digestion followed by agarose gel electrophoresis. This method is more rapid, more reliable and less expensive than currently available methods.