A rabbit model for the study of hypersensitivity to thimerosal was established in order to develop better techniques for screening patient sera and tears for specific antibodies to lens care reagents. Thimerosal (sodium ethylmercury thiosalicylatelate) was successfully coupled to several protein carriers using a water soluble carbodiimide which linked the carboxyl group of thimerosal to free amino groups of the carrier proteins. Thimerosal was also shown to spontaneously react with proteins as detected by the irreversible binding of mercury to the protein carrier. Immunization of rabbits with the chemically coupled thimerosal resulted in the production of antibodies which specifically reacted with thimerosal. The rabbits also manifested delayed and immediate forms of hypersensitivity to the thimerosal conjugates. The ELISA assay for specific serum antibodies was found to be a sensitive, reliable and specific screening tool However, there was no immunological cross reactivity between the chemically coupled thimerosal and the spontaneously coupled thimerosal. Therefore, the epitopes produced by these two reaction mechanisms were probably immunochemically different even though both contained detectable thimerosal derived mercury.