The principle objective of this research was to develop an assay to detect antibodies to hemoglobin adducts in butadiene exposed workers. Demonstration of such antibodies would show the feasibility of using an immune response as an index of toxin exposure. There are many advantages of utilizing antibody detection for this purpose: 1. Antibodies could persist for an appreciable length of time after the exposure, so that detection is conceivably possible after the event. 2. Antibodies can be detected in minute quantities. 3. Antibody assays are ideal for testing of large numbers of samples requiring only minute amounts of blood. 4. Antibody assays are inexpensive. 5. Ultimately, a panel of antigens could be utilized in a microchip array allowing screening for many toxins simultaneously. We used plasma samples from workers exposed to butadiene, and tested them for IgG, IgA and IgM antibodies to a hemoglobin adduct. The antigen, N, N-(2,3 dihydroxybuta1,4,diyl) valine was kindly provided by Dr. James Swenberg, U. North Carolina. We developed an ELISA assay for the detection. IgM antibodies were found in 7 / 19 exposed and 3 / l0 non-exposed workers. IgG antibodies were found in 3/19 exposed and 1 / 10 non-exposed workers. During the course of this study, we had the opportunity to study serums from mice that had received daily exposure to butadiene for a two week period as part of a study conducted by Dr. Vemon Walker at the Wadsworth Institute of the New York State Public Health Department. Two of 15 exposed mice had a strong response to the hemoglobin adduct (OD 405: 0.346 and 0.374). One of 10 non exposed controls also had a positive response, but the response was low (OD 405: 0.107). We conclude that antibody assay is a method which can detect toxin exposure and should be developed further to include a wide range of antigens which would allow mass screening of populations at risk.