We investigated the expression of Ia antigens on T-cells from lung and blood, as a sign of T-cell activation, in 17 patients with active pulmonary sarcoidosis, 12 patients with inactive sarcoidosis, 9 patients with hypersensitivity pneumonitis, and 10 normal control subjects. Lymphocyte subsets were identified by mouse monoclonal antibodies using a peroxidase-antiperoxidase method. Patients with active sarcoidosis and patients with hypersensitivity pneumonitis had a significant increase in Ia+ T-cells in bronchoalveolar lavage fluid compared with that in patients with inactive sarcoidosis and that in control subjects (p less than 0.01). Blood T-cells from the same patients did not show this sign of activation. The highest numbers of Ia+ T-cells were recovered from the lungs of patients with hypersensitivity pneumonitis, indicating the high state of activation of immunoregulatory T-cells in this disease. Additional analysis revealed that in sarcoidosis, Ia+ lung T-cells were exclusively of the OKT4+ helper phenotype, whereas in hypersensitivity pneumonitis, OKT4+ helper as well as OKT8+ suppressor lung cells expressed in part Ia antigens. These observations suggest that different T-cell subpopulations are activated in sarcoidosis and in hypersensitivity pneumonitis.