We investigated the early effects of cigarette smoking in healthy subjects by means of lung lavage, looking at markers of alveolar permeability, the alveolar cell profile, the immunophenotyping of macrophages and lymphocytes, and the level and profile of surfactant phospholipids. Bronchoalveolar lavages (BAL) were performed in 33 healthy subjects [20 nonsmokers (nS), 13 moderate and short-time smokers (S)]. In the acellular supernatants we measured the markers of alveolar permeability (i.e., total proteins, albumin, albumin/urea), the alveolar epithelial lining fluid (AELF), the surfactant amounts and profile, and explored the blood lymphocytes by in vitro exposure. The cell pellet established the alveolar formula and a membrane mapping of macrophages (LFA-1 and HLA-DRII expression) and lymphocytes (CD4, CD8, LFA-1, HLA-DRII expression). We found no significant increase of alveolar permeability in our smokers, but an increased alveolar cellularity (more than 3-fold vs nS, P < 0.05) evenly distributed between sub-populations except for an enhanced number of eosinophils in smokers (P < 0.05 vs nS). Smokers' alveolar macrophages had an overloaded cytoplasm, a decreased percentage of antigen-handling cell expression (HLA DRII: P < 0.05 vs nS) and a low percentage of cell to cell adhesion molecule expression (LFA-1: P < 0.05 vs nS). Smoking history and LFA-1 expression on alveolar macrophages were interrelated. Smokers' alveolar lymphocyte subsets were more often T suppressor cells (CD8+) and had an increased percentage of antigen-presenting cell expression (HLA DRII: P < 0.05 vs nS). Smokers' BAL fluid did not show the inhibitory control of phytohemagglutinin-induced lymphocyte proliferation present in nonsmokers' fluids. Surfactant phospholipid amounts were similar, but phosphatidylethanolamine was raised and the ratio of phosphatidylcholine to sphingomyelin decreased in smokers (P < 0.05 vs nS). We observed specific cellular and biochemical alterations in the lung lavage of short-time smokers. Alveolar macrophage and lymphocyte expression of LFA-1 and HLA-DR II molecules was altered. Smokers' alveolar fluids lost the physiologic regulatory control of T mitogen-induced lymphocyte proliferation. Membrane phospholipids released by cellular damage increased early in tobacco-exposed lung fluids. This profile of alterations may be an early and sensitive marker of smoking-induced lung damage.