A single deep breath is considered the main physiological stimulus for surfactant secretion, and this may be mediated - amongst others- by stretch-induced exocytosis of lamellar bodies (LBs) from pulmonary type II pneumocytes. Ca2+ entry from the bath into the cytoplasm by a single stretch of type II cells in primary culture is a prerequisite for LB fusion with the plasma membrane. Also agonist (ATP)-induced stimulation is accompanied by Ca2+ entry and dramatic changes of type II cell shape and stiffness. Furthermore, single LB fusion events frequently cause LB swelling and subsequent Ca2+ spikes, which spread out from the site of LB fusion. Elevation of the cytoplasmic Ca2+ concentration, in turn, accelerates the opening of fusion pores and facilitates surfactant release into the extracellular space.From these observations we postulate a mainly mechanical cascade of events that couples type II cell stimulation with surfactant release. These mechanisms may be common to stretch- and agonist (ATP)-induced exocytosis.