Accessory function allows antigen-presenting cells to produce sufficient secondary signals for optimum T cell proliferation and interleukin-2 (IL-2) production. Alveolar macrophages are inferior accessory cells compared to monocytes (PBM). We report here that the accessory index (AI) of alveolar macrophages and PBM of patients with lung metastases of solid tumors treated with inhalations of human natural IL-2 (hnIL-2) increased following its administration (P<0.005). The accessory index was significantly elevated from baseline values after 2 weeks of inhalation of 300,000 IU hnIL-2/day (8.2 +/- 10.2 compared to 1.1 +/- 1; P<0.001). The inhalation of 150,000 IU also induced increases in the index (AI = 2.3 +/- 1.9), however, without reaching statistical significance. In addition at 300000 IU IL-2/day a significant increase in the accessory index was observed for PBM (4 +/- 2.5; P<0.05). The indices of PBM and alveolar macrophages prior to inhalation showed a significant negative correlation with the age of the patients (r(s) = -0.5; r(s) = -0.8, respectively; P<0.03 for all comparisons). Our data demonstrate that the inhalational application of hnIL-2 enhances the accessory function of alveolar macrophages and, to lesser extent, the accessory index of PBM, indicating the occurrence of pharmacological immunostimulation.