Calcium channel blockers have recently been shown to improve pulmonary and myocardial preservation. The effect of verapamil on hypothermic lung preservation was investigated using an isolated ventilated rabbit lung perfusion model. In phase 1, preserved lungs were not flushed prior to extraction. Four groups of five animals were studied: group 1 (no verapamil), group 2 (verapamil administration prior to extraction), group 3 (verapamil at reperfusion only), group 4 (verapamil both prior to extraction and at reperfusion). In phase 2, two groups of five animals received pulmonary artery flush with low potassium (4 mmol/L), 2% low-potassium dextran (LPD) solution; group 1 (without verapamil), group 2 (flush and reperfusion with verapamil). As in phase 1, lungs were stored for 30 hr at 10 degrees C prior to reperfusion. In phase 3, the protocol was identical to phase 2, except that the storage time was extended to 48 hr. PO2 (mean +/- SE) of effluent blood in lungs treated with verapamil prior to extraction (122.8 +/- 5.0 mmHg) was significantly increased in comparison with lungs not receiving verapamil (69.0 +/- 3.3 mmHg) or only receiving verapamil at the time of reperfusion (87.1 +/- 11.9 mmHg). Gas exchange after 30 hr storage was equivalent in lungs flushed with LPD with or without verapamil. However verapamil did provide an advantage when preservation times were extended to 48 hr (62.3 +/- 8.5 mmHg, 46.9 +/- 2.3 mmHg). Verapamil administered prior to lung extraction provides better lung function following preservation, but has benefit over LPD flush only with extended periods of preservation (48 hr).