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The frequency of sensitization to environmental antigens changes in different regions. As such, the pattern of sensitivity to common allergens was studied at multiple sites across central Pennsylvania, an area composed of small cities and rural communities, to determine uniqueness of allergies in populations from this area in contrast to allergies as determined by skin testing in large urban centers. The study reported was undertaken to determine allergen variation from an urban population compared with a rural population of a Northeastern state so that environmental avoidance and immunotherapy can be more precisely prescribed. Patient charts were retrospectively reviewed to determine sensitivity to house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cockroach, Penicillium, Aspergillus spp, dog, cat, timothy grass, ragweed, oak, and Alternaria tenuis at five sites in Pennsylvania. All of these sites were classified as "small city" or "rural" for the study. One hundred patient records were examined at each site for the results of allergy testing by the prick puncture, radioallergosorbent test (RAST), or intradermal methods. These small-city and rural data were pooled and compared with that of the National Cooperative Inner-City Asthma Study (NCI-CAS), which included 1286 patients from urban environments. The prevalence of allergy to both species of dust mites, dog, timothy grass, and ragweed was significantly greater in the pooled rural group than in the NCICAS inner-city patients (P < .05). In contrast, sensitivity to cockroach antigens and Alternaria was significantly greater in the NCICAS urban population than in the pooled rural group (P < .05). No statistically significant difference was found between the NCICAS and the pooled rural patients in reference to Penicillium, cat, and oak (P > .05).