To help explain increased recruitment of leukocytes to smokers' lungs, we examined the possibility that the smoke-induced chemotactic activity in lung fluids may be partly complement-dependent. Acute inhalation exposure of rats to smoke from 2R1 Kentucky Reference cigarettes caused an increase in the leukocyte chemotactic activity of their lung secretions (collected by bronchoalveolar lavage 1 h after exposure). Prior depletion of circulating complement, by intravenous administration of purified cobra venom factor 24 h beforehand, prevented the smoke-induced rise in lavage fluid chemotactic activity. Crossed immunoelectrophoretic analysis of lavage C3 from smoke-exposed animals demonstrated a modified form of the molecule with increased electrophoretic (anodal) mobility. When 2 strains of mice, C5-deficient DBA/2 and C5-sufficient BALB/c, were acutely exposed to cigarette smoke, only the C5-sufficient animals (BALB/c) had increased neutrophil chemotactic activity in their lung fluids 1 h after exposure. These results show that the increased chemotactic activity in lung fluids of laboratory animals immediately after acute cigarette smoke exposure is complement-dependent.