Suspensions of rat peritoneal cells were sensitized for either anaphylactic or complement-dependent cytotoxic release of histamine. In both cases the reactivity of the mast cells in vitro appeared to be influenced by the coating of rat immunoglobulin previously acquired in vivo. Sensitization for the complement-dependent release of histamine resulted from the interaction of rabbit anti-rat immunoglobulin antiserum with host IgG on the mast cell. Mast cells from young rats failed to participate in this reaction presumably because of an insufficient coating of IgG. In contrast, cells from young or germ-free rats had a much greater capacity for in vitro passive sensitization by anaphylactic antibody than cells of older rats. In older rats the sensitization sites may have been preempted by anaphylactic antibody directed against indifferent, naturally occurring antigens, or another immunoglobulin may block access to sensitization sites by steric hindrance.