Prior studies comparing skin testing to serum-specific IgE testing for inhalant allergy focused on older technologies or small numbers of allergens. The purpose of this study was to compare ImmunoCAP (CAP) testing to skin prick testing (ST) for 53 inhalant allergens. Subjects > or =18 years old with chronic rhinitis and who had at least 1 positive ST to a 53 inhalant allergen panel underwent testing to an analogous CAP panel. ST was performed with the Quintip device. Using ST as a clinical gold standard, the sensitivity, specificity, positive, and negative predictive values (PPV, NPV) were calculated for CAP for each allergen. Percent agreement between testing methods was also evaluated, and the results were analyzed in association with the subjects' total IgE levels. Two-hundred fifty patients (96 male, 154 female, mean 37.1 years) were enrolled. Mean number of positive ST and CAP results were similar. The ST was more often positive for 69.8% of allergens, and 64% of patients had more positive ST than CAP. Overall, the specificity and NPV (generally 80-90%) of CAP were higher than the sensitivity and PPV. The overall agreement between tests was 80.6%, with 11.7% ST+CAP- results and 7.7% CAP+ST- results. In patients with a total IgE level > or = 200 IU/L, the percentage of positive CAP results for 52/53 allergens was significantly higher with more CAP+ST- results. The performance characteristics of CAP compared to ST vary among 53 inhalant allergens. CAP should be considered complementary, not equivalent, to ST. Total IgE levels should be obtained with serum-specific IgE testing.