Acute [Coccidioides immitis] coccidioidal pleural effusions were studied in 28 patients. Coccidioidal pleural effusion appeared to be secondary to direct spread of contiguous parenchymal infection, rather than to hematogenous dissemination, in more than 90% of these patients. Only 2 of 28 patients had the concomitant development of disseminated infection, and both patients possessed factors known to predispose to dissemination. Because of the excellent prognosis in most patients, therapy in patients with coccidioidal pleural effusion should be expectant. This is true even when substantial increases occur in complement fixation titers; such elevations were frequent in this series. Cultures of pleural biopsy specimens were the most rewarding cultural source in this series, being positive in all 8 patients in whom such biopsy specimens were cultured. Dermal hypersensitivity, including erythema nodosum and erythema multiforme, was common in patients whose clinical course was uncomplicated.