Acute respiratory failure caused by infection with Coccidioides immitis is a rare, usually fatal, event. We report 2 patients who survived acute respiratory failure caused by primary pulmonary coccidioidomycosis. We attribute the severity of illness to a large inoculum of organisms. Their treatment included antifungal therapy with amphotericin B and diuresis to decrease noncardiogenic pulmonary edema. Coccidioidomycosis causing respiratory failure may be more frequent than currently clinically appreciated and may result from primary pulmonary coccidioidomycosis, miliary pulmonary disease, or as part of the multisystem organ failure seen in fungemic patients.