The possible involvement of mast cells in the pathogenesis of lung emphysema is not well described. In the current study, the effect of cigarette smoke on mast cells was investigated in vitro and in vivo. We studied the distribution of mast cells during development of lung emphysema in an animal model for cigarette smoke-induced emphysema. We show that cigarette smoke induced the expression of tryptase and suppressed surface expression of Fc-epsilon-RI and c-kit, and increased the number of tryptase-positive mast cells in the airways. Cigarette smoke induced in vitro TGF-beta production by mast cells. Besides, TGF-beta was increased in BALF of smoke-exposed mice. Neutralization of TGF-beta suppresses induction of tryptase induced by cigarette smoke. To investigate the crucial importance of TGF-beta in the induction of tryptase expression in mast cell cultures by cigarette smoke extracts, we have performed similar experiments in the presence of a TGF-beta-neutralizing antibody. In cell activation experiments positive and negative controls were included. In FACS experiments isotype controls were included to control for a specific binding. TGF-beta expression induced by cigarette smoke increases tryptase expression in mast cells and affects mast cell development, which could be of functional importance in the pathogenesis of lung emphysema.