The effect of calcium and selected calcium antagonists on the lung phospholipid secretion associated with lung distension was examined in newborn rabbits. Lung distension was produced by saline lavage or air inflation in freshly killed pups. Calcium or calcium antagonists were added to the lavage solution. The fractional stimulation of secretion with 1.0 mM calcium was 1.94 +/- 0.28 (p less than 0.01), but ethylene diamine tetraacetic acid (EDTA) did not have the expected inhibitory effect. There was dose-related inhibition of phospholipid secretion induced by the calcium antagonist, lanthanum, the fractional recovery decreasing from 1.0 +/- 0.23 at 10(-5) molar, to 0.43 +/- 0.19 at 0.5 x 10(-4) molar, to 0.22 +/- 0.03 at 10(-4) molar and 0.19 +/- 0.05 at 10(-3) molar (p less than 0.001). This inhibition was significantly reversed by the addition of 10 mM calcium. Although nifedipine and verapamil had no effect, nickel and cadmium also inhibited secretion. Therefore, it is likely that lanthanum acted as a calcium channel blocker, suggesting the importance of extracellular calcium. The observation that intense calcium chelation with ethylene glycol bis-aminoethylether tetraacetic acid-bis-aminophenoxyethane tetraacetic acid (EGTA-BAPTA) had a significant inhibitory effect, supports the conclusion that a superficial calcium pool in the plasma membrane may be an important stimulus for phospholipid secretion during lung distension. The inhibitory effect of neomycin, a drug known to displace superficial calcium, was consistent with this conclusion.