Aggregates of various mammalian beta 2-microglobulin (beta 2m) homologues were tested in binding experiments with group A streptococcal strains of different M types. The binding patterns obtained were similar, suggesting that evolutionarily conserved parts of the beta 2m molecule are responsible for the interaction with group A streptococci. An N-terminally abnormal beta 2m showed binding characteristics similar to those of normal human beta 2m, indicating that the amino-terminal does not participate in this interaction. Aggregates of human IgG Fab fragments, kappa chains and lambda chains, were also analyzed. Whereas several of the beta 2m-reactive M types did not interact with any of these aggregates, all strains binding aggregated Fab, kappa or lambda, also bound aggregated beta 2m. Strains of M types 4, 12, 23 and 53 bound all the tested proteins; M type 1 bound all but IgG Fab, whereas M types 46, 49 and 53 showed affinity for beta 2m and lambda chains only. In inhibition experiments, unlabelled aggregated beta 2m in excess completely blocked the uptake of radiolabelled aggregated IgG Fab, kappa and lambda chains. Conversely, Fab, kappa and lambda aggregates inhibited the binding of radiolabelled beta 2m aggregates. Our results indicate that the differences in reactivity recorded between beta 2m and IgG Fab, kappa and lambda chains, all structurally related, are quantitative rather than qualitative. Thus, a common binding structure for these aggregated proteins on group A streptococci appears probable.