Sarcoidosis is a multisystem granulomatous disorder of unknown origin characterized by the presence of epithelioid granulomata in the affected organs. Histological and clinical similarities between sarcoidosis and tuberculosis caused by M. tuberculosis suggest a shared underlying pathophysiology. However, specific markers are needed. This study examined the differential gene expression pattern in alveolar macrophages of patients with granulomatous disorders. The differential mRNA regulation pattern of alveolar macrophages in the bronchoalveolar lavage of healthy controls was compared to that of patients with sarcoidosis and tuberculosis by means of differential display reverse transcription PCR. Comparative analysis of 2,498 PCR products in controls, sarcoidosis, and tuberculosis revealed a differential regulation of expressed sequence tags in only 6.5%. 1.8% showed a shared expression pattern between sarcoidosis and tuberculosis in contrast to the control. It can be assumed that these alterations are associated with common granulomatous features. In contrast, 3.0% of the amplified sequence tags showed specific up- or downregulation in sarcoidosis and 1.6% in tuberculosis. These data indicate a significant proportion of common granuloma-associated features, independent of the origin of the granulomatous disorder.