Epidemiological investigations of grain workers have suggested the presence of biological hazards in terminal grain elevators. Immunological assessments of the involved individuals, however, have produced inconclusive results. We have recently demonstrated in vitro a potential biological mechanism which could occur in vivo upon inhaling airborne graon dust, thereby constituting a potential inflammatory insult to the respiratory tracts of grain workers. Airborne dusts of similar size distributions generated by transporting grain in terminal grain elevators have been shown to activate the alternative pathway of complement in precipitin-negative pooled normal human serum. These dusts consumed hemolytic complement in a dose-response manner as quantified by both CH100 immunodiffusion and CH50 tube methods. The proactivator of C3 was converted to the activator form in the presence of the chelator EGTA, but conversion was prevented by EDTA. Likewise, serum from guinea pigs genetically deficient in C4, thereby lacking a functional classical complement pathway, showed complement consumption by grain dusts via the alternative pathway. Relative CH50 toxicity ranking of the various dusts was found to be unrelated to the amount of endotoxin present. Of interest, aged settled dust (20-30 years) remained relatively active against the alternative complement pathway as did 15 min aqueous extracts of ground whole rye.