Amiodarone pneumonitis is a serious complication that may lead to fatal lung fibrosis. In an attempt to diagnose this condition as early as possible, the technetium-99m-labelled diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol washout rates of 10 non-smoking normal volunteers (group 1), 10 non-smoking patients on a long-term amiodarone regimen with dilated cardiomyopathy but no congestive heart failure (group II) and 10 patients with amiodarone pneumonitis (group III) were compared. Spirometric measurements, as percentage predicted, were higher in group I than in group III (P less than 0.05). The global mean effective half-lives of 99mTc-DTPA aerosol for both lungs together in minutes were 65 +/- 14, 55 +/- 16 and 27 +/- 4 for groups I, II and III, respectively. Group III values were significantly lower than those of groups I and II (P less than 0.05). Our results demonstrated that amiodarone pneumonitis alters the alveolar-capillary membrane permeability to hydrophilic molecules. The pulmonary clearance of 99mTc-DTPA aerosol is a useful test in the differentiation of patients on a long-term amiodarone regimen without side effects from patients with amiodarone pneumonitis. The test is rapid, easy to perform and has the potential for playing an important role in deciding which patients should discontinue therapy.