The effects of nickel subsulfide (Ni3S2) on the pulmonary immune system were evaluated in cynomolgus monkeys that had been previously immunized and repeatedly challenged with sheep red blood cells in specific lung lobes. After instillation of Ni3S2, at a final dose of 0.06 mumol/g lung, in one immunized and one control lobe of each monkey, bronchoalveolar lavage cells were evaluated for alterations in cell number and function. Neither numbers of antibody-forming cells nor natural killer (NK) cell conjugate formation were altered in immunized lobes of nickel-exposed animals regardless of individual lung lobe nickel exposure. Macrophage phagocytic activity was significantly decreased, and target cell killing by conjugate-forming NK cells was increased in all lobes independent of antigen or nickel exposure in all nickel-exposed animals. Histologic sections of nickel-exposed lobes were characterized by mild focal accumulations of macrophages and lymphocytes within the interstitium and alveoli and by perivenular lymphoid infiltration and follicle formation. We conclude that alveolar macrophages are sensitive to the toxic effects of nickel and that local instillation of Ni3S2 in the subhuman primate lung results in suppression of pulmonary alveolar macrophage function accompanied by a secondary increase in NK cell-mediated killing of target cells.