This study investigates the leukocyte-dependent histamine release (LDHR) from rabbit platelets, a complement-independent mechanism linked to immune complex deposition in acute serum sickness. The LDHR mechanism requires leukocytes but not complement. When washed leukocytes from immunized rabbits are combined with specific antigen and platelets, the platelets aggregate and release histamine. A soluble factor from the leukocytes causes platelet aggregation and histamine release. The presence of LDHR correlates with immune complex deposition in arteries and glomeruli in rabbits, suggesting its role in immune disease pathogenesis. The study found that the antibody responsible for LDHR is IgE. Basophils, identified by electron microscopy, are the leukocytes involved in the LDHR reaction. The soluble platelet-activating factor (PAF) released from sensitized basophils upon antigen addition causes platelet aggregation and histamine release. PAF's stability and recovery depend on the reaction environment. Technical improvements allowed further analysis of PAF and factors in rabbit immunization that consistently produced strong LDHR responses. The LDHR reaction is an IgE-mediated immediate hypersensitivity mechanism involving sensitized basophils. Upon antigen exposure, basophils degranulate, releasing histamine and PAF, which causes platelet aggregation and histamine release. PAF is bound to serum albumin and is stable under certain conditions. The study also links LDHR to immune complex deposition in rabbits, suggesting its role in immune disease pathogenesis. PAF may have other functions beyond platelet activation, including vasopermeability. The findings highlight the importance of LDHR in immune responses and its potential role in allergic and immunologic diseases.This study investigates the leukocyte-dependent histamine release (LDHR) from rabbit platelets, a complement-independent mechanism linked to immune complex deposition in acute serum sickness. The LDHR mechanism requires leukocytes but not complement. When washed leukocytes from immunized rabbits are combined with specific antigen and platelets, the platelets aggregate and release histamine. A soluble factor from the leukocytes causes platelet aggregation and histamine release. The presence of LDHR correlates with immune complex deposition in arteries and glomeruli in rabbits, suggesting its role in immune disease pathogenesis. The study found that the antibody responsible for LDHR is IgE. Basophils, identified by electron microscopy, are the leukocytes involved in the LDHR reaction. The soluble platelet-activating factor (PAF) released from sensitized basophils upon antigen addition causes platelet aggregation and histamine release. PAF's stability and recovery depend on the reaction environment. Technical improvements allowed further analysis of PAF and factors in rabbit immunization that consistently produced strong LDHR responses. The LDHR reaction is an IgE-mediated immediate hypersensitivity mechanism involving sensitized basophils. Upon antigen exposure, basophils degranulate, releasing histamine and PAF, which causes platelet aggregation and histamine release. PAF is bound to serum albumin and is stable under certain conditions. The study also links LDHR to immune complex deposition in rabbits, suggesting its role in immune disease pathogenesis. PAF may have other functions beyond platelet activation, including vasopermeability. The findings highlight the importance of LDHR in immune responses and its potential role in allergic and immunologic diseases.