There is mounting evidence that activated interleukin 2 (IL-2)-releasing lymphocytes play a central role in the immunopathogenesis of sarcoidosis by directing inflammatory reactions and granuloma formation. In the context that a significant proportion of these cells accumulates in the lung and releases mediators, we hypothesized that different immunologically defined stages of sarcoidosis can be identified. A cohort of 89 sarcoidosis patients was allocated to four groups according to the following criteria: stage A, a low number of bronchoalveolar lavage (BAL) lymphocytes (< 20%) without IL-2 release (< 1 unit/ml in BAL cell culture supernatant); stage B, BAL lymphocytes < 20%, with IL-2 release (> or = 1 unit/ml); stage C, BAL lymphocytes > or = 20% with IL-2 release; and stage D, > or = 20% BAL lymphocytes without IL-2 release. Although patients of stages C and D (n = 49) exhibited lymphocytic inflammation, only 20/49 of these patients had activated IL-2-releasing alveolar lymphocytes. BAL of groups A and B showed a low number of lymphocytes, but the lymphocytes were activated in 20/40 patients. Forty-four patients not receiving therapy were reevaluated by pulmonary function tests 8 +/- 1 months after BAL. Progressive disease was found in 9/12 patients of group C and stable or regressing disease in 13/13 patients of group A. These results demonstrate that a combination of BAL parameters can yield prognostic information.