Occupational immunologic lung diseases caused by exposures to substances such as hexahydrophthalic anhydride are significant health problems. It would be useful to identify risk factors, other than exposure, for occupational immunologic lung diseases such as occupational asthma. Our objective was to identify risk factors for development of immunologically mediated disease in workers with respiratory symptoms associated with exposure to hexahydrophthalic anhydride. A medical and immunologic survey study was conducted of 33 employees with respiratory symptoms associated with hexahydrophthalic anhydride exposure. Of the 33 employees with respiratory symptoms, 20 had no immunologically mediated disease. Seven had both immunoglobulin E-mediated and immunoglobulin G-mediated disease, 5 had immunoglobulin E-mediated disease only, and 1 had immunoglobulin G-mediated disease only. Although larger samples would have rendered atopy a statistically significant risk factor (assuming effect replication), the associated effect strength represents less than a 16% improvement versus chance, which is indicative of marginal clinical significance. However, as expected, elevated levels of specific antibodies were statistically and clinically significant risk factors. Development of one type of immunologically mediated disease was highly predictive of development of the other type. In hexahydrophthalic anhydride-exposed employees with respiratory symptoms, development of immunologically mediated respiratory disease is most closely associated with presence of specific immunoglobulin E or immunoglobulin G antibodies. Neither race, age, smoking status, atopy, nor exposure levels emerged as significant risk factors in this symptomatic study population.