Abstract Nile tilapia, Oreochromis niloticus (L.), and channel catfish, Ictalurus punctatus (Rafinesque), were experimentally infected by immersion with three isolates (Lake, DL8O5 and MS91452) of Streptococcus sp. from diseased fish. To enhance infection, the lateral body surface of each fish was scraped prior to bacterial exposure. The Lake and DL8O5 isolates caused exophthalmia, ocular opacity and ocular haemorrhage in some tilapia. Histopathology of these fish revealed; meningitis; polyserositis of heart, liver, spleen, ovary and kidney; splenitis; ovaritis; and myocarditis. Isolate MS91452 induced only mild granulomas in spleen, kidney and ovary of tilapia. The Lake and DL8O5 isolates induced endophthalitis, Channel catfish infected with the Lake and DL805 isolates developed similar eye lesions to tilapia. Histologic lesions caused by all three isolates in channel catfish consisted of meningoencephalitis, mild myocarditis, splenitis and ovaritis, but these lesions were not as severe as in Nile tilapia.