The mechanism of antihamster macrophage serum (AHMS)-induced fusion of hamster macrophages has been investigated using the serum alone or conjugated to ferritin or Sepharose beads. It has been shown that AHMS attaches to and is interiorised by hamster macrophages. When macrophages are brought into contact before AHMS bound to their surface is interiorised, fusion results. The results strongly support the hypothesis that macrophage fusion is the consequence os simultaneous endocytosis of particles or colloids. It is suggested that a similar mechanism underlies the formation of macrophage giant cells in granulomata where closely packed macrophages attach to and interiorise the denatured materials produced in the chronically inflamed environment.