We have studied 15 patients with amiodarone pulmonary toxicity and compared them with five amiodarone patients without evidence of toxic effect. Six of 15 patients who had toxic reactions presented with an acute illness that resembled an infectious disease. While diffuse interstitial disease was frequent on chest roentgenogram, seven of 15 had airspace opacities, and five had well-localized infiltrates. Physiologic changes were not uniformly found. An interstitial pneumonia with foamy alveolar macrophages was the most common pathologic finding. Foamy macrophages were also present in three of five nontoxic patients. Three of three patients who had toxic reactions, and two of five patients without toxic reactions had lamellated inclusion bodies by electron microscopy. We conclude that all features of amiodarone toxicity are protean, and it may mimic infectious diseases. While pathologic changes are often characteristic, neither foamy alveolar macrophages nor lamellated cytoplasmic inclusions reliably distinguish toxic from nontoxic patients. © 1987, American Medical Association. All rights reserved.