A retrospective investigation of 86 asthmatic subjects defined clinical features of irritant-induced asthma and assessed the contributory role of an allergic predisposition. Three categories of asthma were evaluated: (1) occupational asthma due to a sensitizer (11 subjects, 13%); (2) irritant-induced asthma (54 persons, 63%); and (3) not occupational/environmental exposure-related asthma (21 subjects, 24%). Two distinct clinical presentations of irritant-induced asthma emerged: the first was sudden onset (29 subjects) and the second was not so sudden in onset (25 subjects). Sudden-onset, irritant-induced asthma was analogous to the reactive airways dysfunction syndrome. Clinical manifestations began immediately or within a few hours (always within 24 h) following an accidental, brief, and massive exposure. In contrast, for the not-so-sudden-onset asthma subjects, the causative irritant exposure was not brief, usually not massive, continued for >24 h, and the initiation of asthma took longer to evolve. Eighty-eight percent of individuals with not-so-sudden irritant-induced asthma displayed an atopy/allergy status (p<0.01). Some of the atopy/allergy subjects with presumed new-onset asthma were found to have suffered preexisting asthma that had been clinically quiescent for at least 1 year before the triggering exposure (16 persons). We conclude that preexisting allergic/atopy and/or preexisting asthma were significant contributors to the pathogenesis of not-so-sudden, irritant-induced asthma and emphasizes a critical interaction between environmental and host factors in the pathogenesis of asthma.