Numerous attempts have been made in recent years to identify and characterize the immunoglobulin site(s) associated with activation of the complement (C) system. Although there is considerable evidence that this activity can be attributed to the Fc fragment of rabbit antibody (1–8), other findings implicate the pepsin digestion products, i.e., the 5S or F(ab′)2 fragment (9–13). A possible basis for these divergent reports may be that multiple pathways exist for an immunologic attack on the C system. Recent studies in this laboratory with guinea pig immunoglobulins have strengthened this inference (14–17). These experiments disclosed that the hemolytic potency of C was diminished following interaction with either the γ-1 or γ-2 antibody classes, and that different pathways of complement utilization characterized these events. We now extend these observations in experiments whose results indicate that there are dual C interaction sites on the γ-2 guinea pig immunoglobulins.