High intakes of microfilariae of a Guatemalan strain of Onchocerca volvulus by Simulium metallicum proved lethal to a considerable proportion of the flies within 24 hours of taking an infecting blood-meal. The gross histopathological changes resulting from infection were compared in groups of moribund and of apparently healthy flies during this period. The marked morbidity of the flies could be related to certain events occurring in the alimentary tract and haemocoele of the fly soon after ingestion of the parasitized blood. The rapid death of the flies may be ascribed to one or more of the following reasons: (i) reverse migration of numerous microfilariae from the expanded- to the tubular-part of the mid-gut, where they cause serious injury and disintegration of the gut epithelium; (ii) abrasive damage to the stomach epithelial cells by the invading microfilariae with occasional release of the gut contents into the haemocoele; (iii) interruption of the formation of the peritrophic membrane, particularly at its anterior and posterior ends, with subsequent failure of the flies to digest the blood in the stomach; (iv) passage of large amounts of parasitized blood from the stomach backwards into the hind-gut, leading to its mechanical obstruction and (v) invasion and injury of various organs of the fly, among them the ventral nerve-cord, brain, optic nerve, eye, halteres, fat-body and flight musculature by excessive numbers of microfilariae.