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Cutaneous late phase reactions (LPR) in rats can be induced by the intradermal injection of anti-IgE antibody or isolated rat peritoneal mast cell granules. Rat LPR are characterized by neutrophil-rich infiltrates at 2 to 8 hr followed by mononuclear cell-rich infiltrates thereafter. Rat Arthus reactions are histologically similar and are complement (C) dependent. To determine the importance of C in the pathogenesis of rat LPR compared with its role in Arthus reactions, rats were treated with cobra venom factor (CVF) (250 U/kg i.v.), and the effects of this treatment on total hemolytic complement (CH50), C3 titers, LPR, and Arthus reactions were assessed. CVF treatment produced profound decreases in both CH50 (from 197 +/- 20 to less than 1.0 U/ml) and C3 (from 44,240 +/- 2840 to less than 5 U/ml) titers after 6 hr, which persisted through at least 30 hr. The inflammatory intensity of heterologous reverse passive Arthus reactions was significantly decreased in CVF-treated animals. In contrast, the intensity of LPR was unaffected by CVF treatment. Therefore, although LPR and Arthus reactions share certain histologic characteristics, these similarities are not due to a mutual requirement for the presence of C.