The detection of specific antibodies (IgE and IgG) in the sera of some workers exposed to diisocyanates is not always consistent and often is not well correlated with a disease state. This is particularly a concern for the testing of TDI-exposed worker populations where the intensity of the specific antibody response is low. The present study was performed to examine the baseline antibody response in a population with no known exposure to TDI. Sera from 30, non-exposed individuals were screened for specific IgG and IgG4 antibodies using a variety of synthetic antigens. Specific and nonspecific inhibition of antigen binding was performed to determine the specificity of the antibody response. One of the serum samples showed a response greater than two standard deviations above the mean for each of the test antigens. All sera except the latter sample showed generalized antigen recognition that could not be specifically inhibited. These results suggest that within the general population, nonspecific reactions can compromise the specificity of diisocyanate antibody testing.