Imperial Valley, California has become increasingly hot, dry, and polluted over the past decade. Particulate matter (PM) levels are amongst the highest in this State, associated with significantly higher asthma prevalence among children in the region compared to national and state averages. The present study was performed to test the hypothesis that Imperial Valley PM by size and chemical composition might possess allergenic properties following introduction into murine lungs without prior sensitization to a known allergen with size fraction as a determining factor. In acute exposure experiments, BALB/c male mice were administered a single 50-μl oropharyngeal aspiration of nanopure water (H2O; control) or a stock 1 μg/μl PM solution. In sub-acute exposure experiments, male and female mice were treated with a total of six 16.6-μl intranasal instillations of H2O or stock PM solution over the course of 14 days. In all experiments, pulmonary function tests were performed 24 hr after the final instillation followed by necropsies for the collection of biological samples. Inflammatory responses measured via cellularity in histopathological tissue sections as well as significant, marked influxes of eosinophils and lymphocytes were noted in the bronchoalveolar lavage fluid in mice administered PM compared to control. Allergic responses, including airway hyperresponsiveness and significantly increased expression of IL-1ß, were found in male mice exposed to either PM2.5 or ultrafine (PMUF). A combination of all three size fractions of PM from Imperial Valley initiated atopic and asthmatic-like symptoms in the lungs of mice in the absence of additional allergen or preexisting condition.