Pulmonary infection with Rhodococcus equi is rare, and most cases are seen in immunocompromised patients, particularly those with acquired immunodeficiency syndrome. We describe the pathologic features in four cases of culture-positive R equi pneumonia occurring in patients infected with human immunodeficiency virus. All four patients had a solitary cavitary pulmonary mass that was resected (n = 3) or had undergone biopsy (n = 1). Pathologically, all specimens revealed sheets of histiocytes with abundant foamy to eosinophilic cytoplasm with numerous phagolysosomes that were positive for periodic acid-Schiff, Gomori methenamine silver, and Grocott stains. Occasional histiocytes contained Michaelis-Gutmann bodies, diagnostic of malakoplakia. The Michaelis-Gutmann bodies yielded positive results with periodic acid-Schiff, Gomori methenamine silver, Grocott, Giemsa, and von Kossa stains (three of three cases studied) and with alizarin red and Prussian blue stains (two of three cases studied). Many gram-positive coccobacilli within histiocytes and associated with neutrophils were found in one case. Ultrastructural study of one case showed histiocytes containing abundant phagolysosomes with degenerated bacterial components and Michaelis-Gutmann bodies. The latter had a targetoid appearance with variegated phagolysosome cores that were mineralized by deposition of electron-dense spicules surrounded by peripheral rings of granular and membranous material. Based on our observations and reports in the literature, there appears to be a more than coincidental association between pulmonary R equi infection, malakoplakia, and human immunodeficiency virus infection.