Background: Simultaneous exposure to more than one allergen might modify the effect of individual allergens. Objective: The purpose of this study was to investigate the effect of current exposures to mite, cat, and dog allergen and pet ownership on sensitization in adults. Methods: Questionnaires, skin tests, and home visits (Der p 1, Fel d 1, and Can f 1, ELISA; mattresses, living room floors) were performed in 2502 adults. Allergen exposure was treated as a continuous variable and divided into quartiles. To investigate the interaction between allergens, quartiles for 3 allergens were added, creating arbitrary combined exposure categories. Results: In the univariate analysis, mite sensitization was associated with Der p 1 in mattresses (odds ratio [OR], 1.10; 95% CI, 1.01 to 1.19; P = .03) and with Can f 1 in living room floors (OR, 1.08; 95% CI, 1.00 to 1.17; P =.05). In a multivariate regression analysis, Der p 1 in mattresses remained an independent associate of mite sensitization (OR, 1.12; 95 % CI, 1.02 to 1.23; P = .03) and pollen sensitization (OR, 1.23; 95% CI, 1.11 to 1.36; P = .0001). The proportion of subjects sensitized to mite increased significantly with the increasing combined exposure categories (P <.0001). The highest prevalence of sensitization to cat and dog was in the medium combined exposure categories. Cat ownership was associated with a reduced prevalence of sensitization to cats (P = .002) and a reduced prevalence of sensitization to dog (P = .003) but had no effect on sensitization to mite and pollen. Conclusions: Sensitization to dust mites increased with the increasing combined exposure. Cat ownership was associated with a lower prevalence of sensitization to cat and dog but not to mite and grass pollen.