We investigated the biochemical and genetic heterogeneity of protein A from Staphylococcus aureus. SpA genes (spas) of various strains were heterogeneous when detected as DraI and EcoRV fragments of chromosomal DNA. Polymerase chain reaction using primers to detect DNA encoding the IgG-binding domains in spa revealed that they numbered between 2 and 5. Protein A from several S. aureus strains showed two types of reactivities to immunoglobulins in normal canine serum according to the number of active domains.