Four cases of coccidioidomycosis, diagnosed in New Orleans, are described to illustrate the varied clinical presentation of this infection. The first is an immunocompromised elderly patient presenting with a cavitary lung lesion after travel to Utah. The second, a young immunocompetent patient presenting with acute respiratory distress syndrome after moving from Arizona. The third and fourth, young Hispanic immigrants with acquired immunodeficiency syndrome presenting with respiratory distress and sepsis. These are examples of different presentations, depending on immune competency, and illustrate the challenges in making this diagnosis in non-endemic areas. For two of the three patients who died an autopsy was obtained. We present the cases, show radiographic and pathological findings, and review the current literature on coccidioidomyocosis.