Background: The diagnostic possibilities of sensitization to various acid anhydrides are limited because of the lack of standardized allergens for the different test systems. This makes the diagnosis of IgE-mediated sensitization caused by occupational exposure difficult. Methods: We prepared conjugates of human serum albumin with phthalic, maleic, trimellitic, and pyromellitic anhydrides to be used for IgE estimation by enzyme-allergosorbent test, skin prick tests, and nasal and bronchial challenge tests. Nine anhydride workers, who complained of various respiratory symptoms, were studied. Results: Of the nine workers, four had immediate-type skin test responses to one or more conjugates. All four subjects had elevated IgE concentrations in addition to two other workers. Three of six nasal challenges and four of nine bronchial challenges resulted in positive responses. All but one of the positive nasal or bronchial test responses were associated with elevated IgE levels. The seven positive challenge test results included five positive skin test responses. On the other hand, in all but two of the subjects with negative challenge test results, no specific IgE could be detected. In these two subjects the negative results were associated with low levels of IgE, and in one, with the absence of asthma. None of the results of tests with unconjugated anhydrides were positive. Conclusions: Anhydrides investigated in this study can induce IgE-mediated hypersensitivity, which can be diagnosed by using the respective human serum albumin in estimation of specific IgE and in skin, nasal, and bronchial challenge tests. Estimation of IgE was demonstrated to be more sensitive than skin prick testing. (J Allergy Clin Immunol 1995;96:489-94.)