Asthma in the inner-city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner-city adult women to define immune abnormalities associated with asthma and atopy. Blood samples were collected from 509 of 606 inner-city women enrolled in the Urban Environment and Childhood Asthma (URECA) study. We tested for associations between atopy and asthma status and cytokine responses in peripheral blood mononuclear cells incubated ex vivo with a panel of innate and adaptive immune stimulants. Atopic subjects had heightened Th2 cytokine responses (IL-4, IL-5, IL-13) to cockroach and dust mite antigens, tetanus toxoid, and phytohemagglutinin (P<0.05 for all). Differences in cytokine responses were greatest in response to stimulation with cockroach and dust mite. In a multivariate analysis, atopy was broadly related to increased Th2-like responses to all antigens and PHA, while asthma was only weakly related to mitogen-induced IL-4 and IL-5 responses. There were few asthma or allergy-related differences in responses to innate stimuli, including IFN-α and IFN-γ responses. In this inner-city adult female population, atopy is associated with enhanced Th2 responses to allergens and other stimuli, and there was little or no additional signal attributable to asthma. In particular, these data indicate that altered systemic interferon and innate immune responses are not associated with allergies and/or asthma in inner-city women.