OBJECTIVE: To estimate the incidence of Churg-Strauss syndrome (CSS) among a large population of asthma drug users. METHODS: A retrospective study was conducted among patients who had been dispensed asthma drugs at 3 managed care organizations. Adults who received >or =3 dispensings of an asthma drug during any consecutive 12-month period between January 1, 1995 and June 30, 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, and inpatient and outpatient diagnoses and procedures was obtained from automated databases. Chart reviews were performed on persons identified by combinations of diagnostic and billing codes indicative of CSS. A rheumatologist reviewed abstracted information on all subjects; those who met >or =2 American College of Rheumatology criteria for CSS were reviewed by 2 clinical experts. Each clinical expert independently rated the cases; disagreements were resolved by consensus. Cases classified as having ‘probable/definite’ CSS were included in these analyses. The incidence of CSS was estimated overall and according to patient gender, age, and calendar year. RESULTS: From a population of 184,667 asthma drug users contributing 606,184 person-years of exposure, 21 incident cases of CSS were identified (overall incidence of 34.6 per million person-years; 95% confidence interval 21.4 to 53.0). Incidence rates did not differ by gender and age group. The incidence rates for 1995, 1996, 1997, 1998, 1999, and the first 6 months of 2000 were 0, 22, 52, 75, 14, and 14 per million person-years respectively. CONCLUSIONS: Results from this population-based study suggest a somewhat lower incidence of CSS in asthma drug users than previously reported and provides important information as to the risk of developing CSS from a population-based perspective.