Light-microscopic and ultrastructural examinations of megalocytic interstitial nephritis, xanthogranulomatous pyelonephritis, and malakoplakia of the kidney were compared. The cases of megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis represent the first reported electron-microscopic studies on human kidney of these diseases. The study confirmed the presence of a polymorphous cellular infiltrate with predominate histiocytes containing crystalloid material in the case of megalocytic interstitial nephritis; a polymorphous cellular infiltrate with histiocytes predominating in the case of xanthogranulomatous pyelonephritis; and macrophages containing Michaelis-Gutmann bodies in the case of malakoplakia. The characteristic sites of involvement within the kidney by each of the three lesions are discussed. It is believed that the lesions are distinct entities, but related to one another, and represent varied and unusual host responses to inflammation.