The respiratory health of 277 workers in a new toluene diisocyanate (TDI) manufacturing plant was studied prospectively during 5 yr of exposure. Personal TDI monitors were used to continuously measure peak and 8-h time-weighted average (TWA) concentrations in over 2,000 samples. Longitudinal change in pulmonary function was assessed in 223 men in whom 3 or more data points allowed construction of individual slopes of annual change. Regression of annual change on smoking (pack-years), atopic status, and cumulative TDI exposure dichotomized at 68.2 parts per billion (ppb) months into low and high exposure groups showed significant effects of smoking on spirometric tests and lung volumes. After adjusting for pack-years of smoking, the 74 men in the high cumulative TDI exposure category had significantly larger declines in FEV1, %FEV, and FEF25--75% than did the 149 men in the low category. Annual change in FEV1 was then examined in 6 smoking-exposure categories: in never smokers, average annual decline was 38 ml/yr greater in those with higher cumulative TDI exposure. Current and previous cigarette smokers did not show this effect of cumulative TDI exposure. Analysis of FEV1 change by time above 20 ppb TDI yielded a similar result in never smokers, a 24 ml/yr excess average decline attributable to longer time above 20 ppb. In current cigarette smokers, those with longer time above 20 ppb had excess decline of 18 ml/yr (42 versus 24 ml/yr). our low and high cumulative exposure groups spent 2 and 15%, respectively, of their working time above 5 ppb TDI. The different health effects observed in these groups supports the NIOSH-recommended standard of 5 ppb TDI as an 8-h TWA.