In an attempt to elucidate the nature of the abnormal vessels in pseudopyogenic granuloma, we performed enzyme histochemical analysis of 10 lesions and correlated them with electron microscopic findings in four lesions. The dermal vessels of pseudopyogenic granuloma possess voluminous endothelial cells demonstrating marked activity of various hydrolytic and respiratory enzymes. The alkaline phosphatase activity, however, is characteristically faint or absent. Electron microscopy reveals that mitochondria and the other common cytoplasmic organelles are abundant in the hypertrophic endothelial cells, probably reflecting increased metabolic cellular activity, whereas specific endothelial granules (Weibel-Palade bodies) are generally sparse in these abnormal cells. Other notable features occurring in several endothelial cells are cytoplasmic vacuolation and the acquisition in the subnuclear zone of dense bodies associated with fine actin-like filaments, 55 to 75 A thick. The latter change is interpreted as evidence of endothelial contraction. Classification of the abnormal dermal vessels using available criteria has proved difficult, but it is suggested that they arise predominantly from the venous side of the microcirculation and are mainly postcapillary venules, although involvement of both larger and smaller caliber vessels also occurs.