Abstract The cytosolic Ca 2+ concentration ([Ca 2+] i) affects many cell functions, including the modulation of ion channel activity. In this study patch clamp experiments using primary cultures of fetal distal lung epithelium (FDLE) demonstrated that the elevation of [Ca 2+] i modulated a 25pS amiloride-blockable non selective cation (NSC) channel's ion selectivity and sensitivity to amiloride. An elevation of [Ca 2+] i from 0.1 μM to 1mM both increased open probability (P o) and decreased the ratio of the premeability to Na to the permeability to K (P Na P K) from 1.96±0.11 (SEM, n= 6) to 0.88±0.04 (n= 6). Within the range of [Ca 2+] i from 0.1 μM to 100μM amiloride (0.5 μM) decreased P o, however amiloride (0.5 μM) no longer affected P o of the NSC channel when [Ca 2+] i was increased to 1mM under physiologic membrane potentials. A β adrenergic agonist (terbutaline, 10μM) increased P o in cellattached patches from almost 0 (P o< 0.01; n= 9) to 0.39±0.09 (n= 9) and [Ca 2+] i from 40±6nM (n= 9) to more than 1μM. This suggested that amiloride-blockable NSC channel activity and ion permeability are modulated by changes in [Ca 2+] i near physiologic membrane potentials and a β adrenergic agonist increases [Ca 2+] i to more than 1μM (unlike other epithelial including adult alveolar cells) which is associated with activation the NSC channel.