Pulmonary coccidioidomycosis is caused by inhaling airborne arthroconidia of Coccidioides, a soil-dwelling fungus endemic to the desert southwestern United States. Although uncommon, disseminated coccidioidal infection can be associated with well-defined risk factors, such as cell-mediated immunodeficiency, certain racial heritages (e.g. African or Filipino), male sex, or pregnancy. Before widespread use of computed tomography (CT), the presence or persistence of mediastinal lymphadenopathy was postulated to be a risk factor for disseminated coccidioidal infection. To investigate the use of CT scanning to identify the presence of mediastinal lymphadenopathy in patients with pulmonary coccidioidomycosis, and to correlate such lymphadenopathy with disseminated coccidioidal infection, we performed a retrospective review of patients with pulmonary coccidioidomycosis who were evaluated by chest CT. Two radiologists independently interpreted 150 CT scans from patients with pulmonary coccidioidomycosis. Forty-nine patients met CT criteria for mediastinal lymphadenopathy, whereas 101 patients did not. Disseminated coccidioidal infection was observed in 5 (10%) of the 49 patients with mediastinal lymphadenopathy and in 6 of the 101 (6%; P = .34) without such adenopathy. Among patients with coccidioidomycosis, patients with mediastinal lymphadenopathy, as assessed by CT, had a higher rate of disseminated infection, but the difference was not statistically significant.