Pulmonary arteries and veins of 14 dogs in phases of heartworm disease (Dirofilaria immitis infection) were examined by scanning electron microscopy. Two dogs were infected with D immitis microfilaria only, whereas 12 dogs were infected with adult D immitis. Seven of the dogs infected with adult worms were untreated. Two of these 7 dogs had natural infections of unknown duration introduced by mosquito bite, whereas 5 were experimentally infected for 30 days. The remaining five dogs were experimentally infected for 1 year and had worms removed by drug therapy. These five dogs were maintained 12 months after treatment. Arteries and veins from dogs infected with microfilaria had a continuous sheet of endothelial cells. Arterial endothelium from the seven nontreated dogs infected with adult heartworms exhibited swirling patterns, pore formation, and separation of intercellular junctions. Arteries from all dogs had numerous endothelialized villus protrusions; veins had similar, less extensive changes. Arteries and veins from experimentally infected dogs were similar to naturally infected dogs, indicating the infection procedure produced lesions similar to that normally seen in heartworm disease. The extent of vascular lesions was reduced in four of the five treated dogs that had been infected with adult worms. Adult worms, not microfilaria, may produce the vascular lesions seen in heartworm disease. Lesions will regress if worms are removed from the circulation. Lesions may be caused by generation of humoral factors initiated by the presence of adult worms.