Three cases of pyogranulomatous cephalic osteochrondritis of intensively reared rainbow trout, Oncorhynchus mykiss (Walbaum), and Atlantic salmon, Salmo salar L., in Canada and Chile, respectively, were examined for histopathological and bacteriological changes, and by using immunohistochemistry. Bilateral exophthalmia and intraocular haemorrhage were the most common gross lesions seen in the Ontario fish. Histologically, the major pathological changes seen in all cases involved the developing bone and cartilage of the head region, including the eye. Necrosis and pyogranulomatous inflammation of the scleral cartilage (necrotic scleritis) were the major ocular changes. Similarly, lysis of cephalic cartilage and immature bone, accompanied by pyogranulomatous inflammation, usually progressing to fibrosis, were the most common lesions associated with the cranial changes in both the rainbow trout and Atlantic salmon. Routine histological staining, including special stains, failed to reveal the presence of pathogens associated with these lesions. However, immunohistochemical staining of representative sections from all cases with rabbit anti-Flexibacter psychrophilus serum (ATCC 49510) demonstrated significant numbers of antigenically related bacteria within the leading edge of some of the scleral and cephalic osteochondritic lesions. Axenic cultures of Flexibacter psychrophilus were recovered from the eye lesions of the rainbow trout, but it was not possible to reproduce ocular lesions experimentally. However, mortality was produced following intramuscular injection of rainbow trout with bacteria.