BACKGROUND: Specific bronchial reactivity to occupational agents may decline after exposure in the workplace ceases leading to falsely negative specific inhalation challenges. A study was carried out to assess prospectively whether increases in nonspecific bronchial hyperresponsiveness could be useful in detecting the bronchial response to occupational agents during specific inhalation challenges. METHODS: Specific inhalation challenges were performed in 66 subjects with possible occupational asthma due to various agents. After a control day the subjects were challenged with the suspected agent for up to two hours on the first test day. Those subjects who did not show an asthmatic reaction were rechallenged on the next day for 2-3 hours. The provocative concentration of histamine causing a 20% fall (PC20) in the forced expiratory volume in one second (FEV1) was assessed at the end of the control day as well as six hours after each challenge that did not cause a > or = 20% fall in FEV1. The subjects who had a significant (> or = 3.1-fold) reduction in PC20 value at the end of the second challenge day were requested to perform additional specific inhalation challenges. RESULTS: The first test day elicited an asthmatic reaction in 25 subjects. Of the other 41 subjects five (12%, 95% confidence interval (CI) 4% to 26%) exhibited a > or = 3.1-fold fall in the PC20 value after the inhalation challenge and developed an asthmatic reaction during the second (n = 3) or third (n = 2) challenge exposure. The offending agents included persulphate (n = 1), wood dust (n = 2), isocyanate (n = 1), or amoxycillin (n = 1). These five subjects had left their workplace for a longer period (mean (SD) 21 (14) months) than those who reacted after the first specific inhalation challenge (8 (11) months). CONCLUSIONS: The increase in non-specific bronchial hyperresponsiveness after a specific inhalation challenge can be an early and sensitive marker of bronchial response to occupational agents, especially in subjects removed from workplace exposure for a long time. Non-specific bronchial hyperresponsiveness should be systematically assessed after specific inhalation challenges in the absence of changes in airway calibre.