Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis that characterize the disease. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied at 6-month intervals over 10.1 +/- 1.6 months with bronchoalveolar lavage, 67Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In this group of patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of all lung effector cells and/or 67Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and 67Ga scan positive, 20% of all observations). However, the alveolitis can be unstable; 75% of all episodes of high intensity alveolitis spontaneously reverted to low intensity, whereas 12% of all episodes of low intensity alveolitis spontaneously reverted to high intensity. Furthermore, conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status; the low intensity and high intensity groups were indistinguishable by usual criteria (p greater than 0.3, all comparisons). Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was "split," i.e., 67Ga scans positive and T-cells low (39%) or 67Ga negative and T-cells high (8%). In fact, 79% of all patients had either a positive 67Ga scan and/or high lung T-cells at least once during the study period, suggesting that most untreated patients with sarcoidosis without extrapulmonary symptoms often have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter 87% of the time. In contrast, a low intensity alveolitis episode was followed by functional deterioration only 8% of the time. Strikingly, while the alveolitis parameters (lavage and 67Ga scanning) clearly predicted prognosis, clinical, roentgenographic, and physiologic tests could not distinguish those patients who would subsequently deteriorate functionally. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.