The aim of this study was to investigate the relationship between release of tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages (AM) and the phenotypic characteristics of bronchoalveolar lavage (BAL) cells in sarcoidosis. We studied the spontaneous release of TNF-alpha by AM in vitro and the phenotypic characteristics of freshly recovered BAL T-cells and AM in 31 individuals (13 with active sarcoidosis, nine with inactive sarcoidosis, and nine normal controls). TNF-alpha was measured by enzyme-linked immunosorbent assay (ELISA) in supernatants from unstimulated AM after 24 h culture. Phenotypic markers of BAL cells were determined by an immunocytochemical assay. AM of patients with active sarcoidosis released more TNF-alpha (1,355 +/- 133 pg/ml/ 10(6) AM/24 h) than those of the inactive group (651 +/- 142 pg/ml/10(6) AM/24 h) or the normal controls (425 +/- 121 pg/ml/10(6) AM/24 h), with p < 0.001 for both comparisons. The amount of TNF-alpha released correlated positively with the percentage expression of CD4 (r = 0.72) and CD25 (r = 0.70) by lymphocytes, and of CD14 (r = 0.63), VLA-4 (r = 0.59), FRD1 (r = 0.67) and 27E10 (r = 0.67) by AM, with p < 0.001 for all correlations. In conclusion, this relationship suggests that these antigens may be considered as cellular activation markers, and that some of these AM antigens may indirectly characterize the AM phenotype that is capable of producing TNF-alpha.