The diagnosis of isocyanate-induced occupational asthma can be made by exposing subjects to isocyanates in small challenge rooms. There are, however, several pitfalls inherent in this procedure. Isocyanate concentrations may not remain stable throughout the exposure and may exceed the recommended TLV ceiling of 20 ppb. This can induce irritant or unduly severe bronchial reactions. To overcome these problems, a closed-circuit apparatus for generating isocyanates in a gaseous form was developed; it was assessed in 20 subjects suspected of having isocyanate-induced asthma. Subjects were tested using both the small challenge room method and the new closed-circuit method in a randomized sequential way. Isocyanate concentrations were more stable with the closed-circuit apparatus than with the challenge room method (mean of individual variance of 6.3 and 61.8, respectively; p less than 0.001). The percentage of the total exposure time during which concentrations were above 20 ppb was reduced from 11.3 to 4.5% (p less than 0.001). The two methods yielded the same number of positive and negative responses, except for one subject who did not have a positive reaction when tested with the challenge room method. The pattern and magnitude of asthmatic reactions were similar for both methods. However, the duration of exposure was shorter with the challenge room method than with the closed-circuit methods (p = 0.04).