A screening program was undertaken at a research and development facility of a large toluene-diisocyanate (TDI) manufacturing corporation. The purpose was to determine the occurrence of antibodies to TDI in selected worker populations. Sera were obtained at 6-mo. intervals from 103 employees exposed for 6-24 mo. to ambient workplace concentrations of TDI (.ltoreq. 0.02 ppm). With the use of RAST (radioallergosorbent test) containing p-tolyl isocyanate-human serum albumin as antigen, no tolyl-reactive IgE antibodies were detected in sera when workers were exposed only to ambient TDI concentrations. Workers (20) had acute exposures to TDI as a result of spills or splashes. Antibody responses developed in 3 of 4 individuals whose acute exposures were accompanied by immediate respiratory symptomatology and a decrease in FEV1 [forced expiratory volume in 1 s] of .gtoreq. 20%. An antibody response developed in 1 of 9 workers and immediate respiratory symptoms but no spirometric changes upon acute TDI exposure. No serologic response developed in the remaining workers whose acute exposure resulted in delayed-onset respiratory symptomatology without spirometric changes or who were asymptomatic at exposure. In persons developing antibodies, an increase in tolyl-reactive IgE was observed within 2 mo. of exposure. Routine serologic screening of workers for tolyl-reactive antibodies may be of value in confirming suspected isocyanate exposure and in providing an early warning of develooing TDI hypersensitivity.