Biallelic polymorphisms in the promoter region of the TNF-α gene (TNFA) and in the first intron of the TNF-β gene (TNFB) have been associated with variation in TNF-α production and with susceptibility to severe diseases. Among other functions, TNF-α plays a pivotal role in regulatory aspects of granuloma formation and sustenance. In sarcoidosis, a systemic granulomatous disorder of unknown aetiology, the clinical course of the disease has been associated with the patient's individual capacity of spontaneous TNF-α production by alveolar macrophages. We determined theTNFAandTNFBpolymorphisms in 101 patients with pulmonary sarcoidosis and 216 healthy blood donors. A highly significant shift to the more uncommonTNFA2 allele was found in the Löfgren syndrome patient group, which represents the acute form of the disease with frequent spontaneous remission. The results show that gene frequencies of theTNFAgene variation are significantly different within the clinical forms of sarcoidosis, indicating that genetic predisposition for TNF-α production may play a role in the pathogenesis of the disease.