Spontaneous pneumothorax associated with Pneumocystis carinii pneumonia (PCP) in AIDS patients has been reported with increasing frequency; however, little is known about the causative histopathology. In the past year, we treated three patients with documented PCP subsequently complicated by multiple spontaneous pneumothoraces. All patients underwent open surgical repair. In contrast to traditional pathologic findings of PCP in AIDS, histologic sections of lung from each patient consistently demonstrated an extensive interstitial inflammatory process with destruction of lung tissue primarily involving the periphery of the lung. Subpleural necrosis with bleb formation as well as bullous changes persisted even in the absence of an alveolar filling process. We conclude that the mechanism for pneumothorax in PCP is spontaneous rupture of necrotic lung tissue occurring in a subgroup of AIDS patients in which the interstitial inflammatory response to Pneumocystis has been accelerated.