Small-granule endocrine cells differentiate in airway epithelium of intact and cultured fetal rat lungs. We noted that the cells store calcitonin gene-related peptide (CGRP) in vitro as well as in vivo and used the ionophore A23187 to test the effects of calcium on peptide secretion in this system. Lungs of 14-day and 15-day fetal rats, organ cultured for 6-9 days, were divided into groups of 5 explants each and incubated for 15 min at 37 degrees C in the basic medium containing 0 mM, 1 mM, or 10 mM CaCl2, with or without 8 microM A23187, or 10 mM EGTA. Intracellular CGRP in these explants was quantified by supraoptimal dilution peroxidase immunocytochemistry (Springall et al.: J. Pathol. 155:259-267, 1988): counts were made of endocrine cells stained with a 1/60,000 dilution of anti-CGRP and repeated on the same sections after restaining with antibody diluted at 1/1,000. Results, analyzed by Chi-square test, were expressed as % cells stained with antibody at 1/60,000 vs. those stained at 1/1,000. Immunoreactivity for CGRP was significantly reduced by A23187 in the presence of high extracellular Ca2+ (10 mM), the inference being that these cells secrete peptide hormones in response to Ca2+ influx across the plasma membrane. The organ cultures evidently can be used to assess certain physiological responses of lung endocrine cells in an accessible, relatively organotypical setting.