It has been shown that alveolar macrophages (AM) are able to modulate lymphocyte proliferation in vitro. The purpose of this study was to evaluate the effect of AM on the proliferation of autologous peripheral lymphocytes (APL) in patients with interstitial lung disease (ILD) compared to controls. Thirty patients were investigated: eight with idiopathic pulmonary fibrosis (IPF), nine with sarcoidosis(SA), seven with rheumatoid arthritis (RA) and six controls (CO). AM and APL were co-cultured at an increasing macrophage/lymphocyte ratio: 1%, 10%, 20% and 50%. A dose-dependent effect was observed and related to the number of AM added to APL, enhancing at low ratios and suppressing at high ratios. Suppression of proliferation by 50% AM differed in the four groups tested: 94.6% (92-98) in IPF, 73.0% (49-100) in SA, 43% (25-57) in RA, 32.4% (22-41) in the CO (P less than 0.01, P less than 0.05, and P0.05 respectively, compared to CO). Suppressive cell activity of AM from patients with ILD was higher than suppressive cell activity of the CO group. Suppression with 10% of AM in ILD group was 18% (2.2-62) compared with 2.58% (-13-17) in the CO group (P less than 0.05). 20% AM in ILD group showed 35% (3-76) suppression in comparison with 9.76% (-11-27) in the control group (P less than 0.01), 50% AM in ILD have a suppressive activity of 71% (25-100) in contrast to 32.4% (22-41) in control (P less than 0.01). In conclusion, AM from patients with interstitial lung diseases have a significantly stronger suppressive effect on the proliferation of autologous peripheral lymphocytes than controls. This is a new aspect of the study of activation of AM in these kinds of disorders.