Inhalation of asbestos fibers is associated with a marked increase in the risk of developing pulmonary malignancy, particularly bronchogenic carcinoma. As natural killer (NK) cells are specialized lymphocytes that are considered to have an important in vivo role in the recognition and destruction of malignant cells, we examined the capacity of asbestos fibers (chrysotile, amosite, and crocidolite) to interfere with the NK activity of nylon wool-nonadherent, human blood lymphocytes (51Cr-release assay, K562 target cells, 14 h effector-to-target ratio = 50:1). Final asbestos concentrations used were 1 to 1,000 micrograms/ml. None of the fibers altered spontaneous target cell lysis or lymphocyte viability. All types of asbestos suppressed NK activity in a dose-dependent fashion. This effect was most marked with chrysotile, which exerted a profound inhibitory effect on blood NK cell activity; at 100 micrograms/ml, NK activity was inhibited 84 +/- 2% (p less than 0.001). The suppressive effects of asbestos were exerted directly on the NK cells (large granular lymphocytes, 91 +/- 2% inhibition at 100 micrograms/ml; p less than 0.001). Exposure of lymphocytes to recombinant interleukin-2 (IL-2, 150 units/ml) for 24 h prior to exposure to asbestos restored the level of activity to 99 +/- 6% of the original value (p less than 0.001), and lung lymphocytes that were exposed to IL-2 in vivo (active sarcoidosis) were resistant to suppression by asbestos. Similar results were observed in a group of patients with asbestosis. This suppression of NK activity may contribute to the increased susceptibility of asbestos-exposed persons to the development of pulmonary malignancy.