The aim of this study was to evaluate the release of neuroendocrine (NE) products into the pulmonary circulation during intermittent hypoxia (IH) in isolated buffer-perfused and ventilated rat lungs. Isolated single-pass perfused rat lungs were repeatedly ventilated with hypoxic (2% O(2)) and normoxic (21% O(2)) gases for 5-min intervals. Perfusate collected during the study was analysed for bombesin-like-peptides (BLPs) and serotonin. In addition, immunohistochemical evaluation of the neuropeptides calcitonin gene-related peptide (CGRP) and chromogranin A (CgA) in the lung was performed. During IH, perfusate levels of BLPs decreased compared to lungs ventilated with normoxic gas only. After 15 min of IH, perfusate levels of BLPs were significantly lower than at corresponding time in normoxic lungs (2.6+/-0.7 pg ml(-1) versus 9.2+/-1.9 pg ml(-1), p=0.036). No significant difference between the study groups was observed in perfusate levels of serotonin. Immunohistochemical evaluation of the lungs revealed significantly increased number of pulmonary NE cells immunoreactive for CGRP in IH ventilated lungs compared to controls (10.1+/-1.5 neuroepithelial bodies (NEBs) (cm(2))(-1) versus 5.0+/-1.5 NEBs (cm(2))(-1), p=0.032). No change in the immunoreactivity for CgA was observed. The present study suggests that intermittent periods of hypoxia are associated with a rapid physiological modulation of the release of NE products into the pulmonary circulation in an isolated rat lung model.