Complement-fixing antibodies (CFA) to a panel of microorganisms commonly associated with respiratory disease were measured in a number of agricultural populations. The panel included Mycoplasma pneumoniae, influenza viruses A and B, parainfluenza virus types 1, 2, and 3, adenovirus, and respiratory syncytial virus. The agricultural populations were grouped according to a clinical history of farmer's lung disease (FLD) and the presence of antibodies to the thermophilic actinomycetes (TA). Farmers with precipitating antibody activity to one or more of the TA (groups I and II) demonstrated a greater frequency of CFA to M. pneumoniae and parainfluenza virus types 1, 2, and 3 than those groups without antibody to the TA, but the level of CFA was not higher in the positive subjects. Immunoglobulin levels were also elevated in groups I and II when compared to the control groups. Unlike IgG and IgM, IgA was elevated only in the farmers who had a clinical history of FLD (group I) but not in farmers without a clinical history. The results suggest that farmers who develop FLD are exposed to a wider variety of pathogens than are other farmers, but do not respond in an accelerated manner.