To evaluate the mechanisms responsible for anergy in sarcoid patients, we studied the ability of highly purified lavage and blood T lymphocytes from control subjects and patients with sarcoidosis to proliferate in response to recall antigens, and compared the results of antigen-induced lymphocyte proliferation with the clinical characteristics of the patients. Both blood and lavage T lymphocytes from all control subjects proliferated in response to purified protein derivative (PPD) and candida antigens, and no significant difference was observed comparing the proliferation of lymphocytes from the two sources. The antigen-induced proliferation of blood and lavage T lymphocytes from sarcoid patients was reduced compared with that of the corresponding cell populations from normal subjects (p less than 0.01 for PPD, Candida, and tetanus), and the proliferative response of sarcoid lavage lymphocytes was significantly lower than that of blood T lymphocytes from these patients. No evidence for inhibition of T lymphocyte proliferation by accessory cells (blood monocytes) or CD8+ T lymphocytes was observed, and the refractory state could not be overcome by adding exogenous recombinant human IL-2 or IL-4. An inverse correlation was observed between the PPD-induced proliferation of sarcoid lavage T lymphocytes and criteria associated with "active" disease, including lymphocytes/ml lavage fluid (p less than 0.003), 67Ga uptake (p less than 0.005), and serum angiotensin converting enzyme activity (p less than 0.005). Lavage lymphocytes from patients studied early in the course of the disease proliferated better than those from patients with more long-standing disease.(ABSTRACT TRUNCATED AT 250 WORDS)