A chronic spastic myelopathy associated with HTLV-I infection (HTLV-I-associated myelopathy: HAM) shows subclinical pulmonary involvement with bronchoalveolar T lymphocytosis. In the present study, we investigated 18 patients with HAM: five HTLV-I carriers without myelopathy and 13 normal control subjects seronegative for HTLV-I to determine if soluble IL-2 receptors (IL-2R), a marker of lymphocyte activation, were increased in serum and bronchoalveolar lavage (BAL) fluid from HAM patients. Serum IL-2R levels were significantly increased in patients with HAM as compared to normal control subjects (HAM versus control subjects: 633 +/- 395 versus 278 +/- 53 U/ml, p less than 0.01). There was also an increase of serum IL-2R levels in one of five HTLV-I carriers. BAL levels of soluble IL-2R were low but detectable in four normal control subjects and in one HTLV-I carrier. In HAM patients, however, soluble IL-2R levels in BAL fluid were remarkably elevated (173 +/- 110 U/mg of albumin) and were nearly 13 times higher on average than in serum (BAL fluid/serum ratio: 13 +/- 10). In patients with HAM, lavage IL-2R levels correlated well with the number of T lymphocytes (CD3+ cells) and CD4+ cells in BAL fluid (p less than 0.01). Furthermore, BAL lymphocytes obtained from HAM patients synthesized DNA spontaneously when cultured in vitro. These results suggest that, in HAM, T lymphocytes increased in the lung are activated locally to produce soluble IL-2R. Based on the results of this study, we conclude that immunologic mechanism(s) may play an important role in the development of pulmonary lesions in HAM patients.