Human myeloma proteins, γ2a, γ2b, γ2c, γ2d and γA, normal γA-globulin and γM-globulin from normal individuals and from Waldenstrom macroglobulinemia patients were aggregated by coupling with bis-diazotized benzidine. The aggregates and the untreated proteins were studied for complement-fixing properties and skin reactivity in normal guinea pigs. Neither untreated nor aggregated γ2d- and γA-globulins showed either activity. The other immunoglobulins, e.g., γ2a, γ2b, γ2d and γM, induced C′ fixing properties upon aggregation. The results were confirmed by C′1 fixation tests. The aggregated γ2b- and γ2c-globulins induced increased permeability of guinea pig skin capillaries, whereas neither aggregated γ2a- nor γM-globulin did. These activities of aggregated γ-globulins were independent of types of light chains and of the presence of Gm factors (a) (b) and (f). The results indicate that the heavy chain structures which are essential for C′1 fixation are different from those involved in fixation of the γ-globulin molecules to guinea pig tissues for passive sensitization.