Cotton grown in Stoneville, Mississippi and harvested by three different methods was examined for anticomplementary activity in human serum in vivo. Subjects exposed to cotton dust in a model cardroom for six hours showed changes in C3c and CH50 after exposure to closed boll harvested, bract removed cotton dust when compared with a group of normal, unexposed controls. Decreases in C3c, :C4, and C3A were associated with decreases in FEV1 after exposure to closed boll harvested bract intact cotton dust. The data from this preliminary study suggest in vivo associations between inhalation of cotton dusts and complement which appear to be independent of endotoxin contamination. These findings suggest a relationship between cotton dust inhalation and complement-mediated respiratory impairment.