Streptococcal infections of fish have been reported from various parts of the world, including the Far East, the United States, South Africa, Australia, Israel and Europe. Classification of Gram-positive cocci (DNA-DNA hybridization studies coupled with 165 sequencing) has shown that at least five different defined species are pathogenic to fish, e.g. Streptococcus iniae (syn. S. shilot), Streptococcus difficile, Lactococcus garvieae (syn. Enterococcus seriolicida), Lactococcus piscium and Vagococcus salmoninarum. "Streptococcosis" of fish should therefore be regarded as a complex of similar diseases caused by different genera and species of Gram-positive cocci, each capable of inducing CNS damage, as well as various degrees of multisystem organ involvement. Panophthalmitis ("pop-eye") and meningitis/meningoencephalitis are the sole findings in trout infected by S. iniae and in tilapines infected by S. difficile. In contrast, L. garvieae-infected trout bear a systemic hyperacute infection with diffuse haemorrhages. Therapeutic measures are generally ineffective. Development of vaccines is therefore essential to control these diseases. In our studies, trout were vaccinated intraperitoneally with whole-cell formalin-inactivated S. iniae and L. garvieae and tilapines with whole-cell formalin-inactivated and acellular S. difficile extract. Under laboratory conditions, S. difficile-vaccinated tilapines were protected against a challenge of 100 LD50s. Protection was correlated with the development of specific agglutinins. Western blot analysis supported the hypothesis that only a few proteins act as protective antigens. S. iniae autovaccines were effective in preventing the disease in rainbow trout in Israel. Under field conditions, fish vaccinated at 50 g were protected for over four months. The qualitative analysis of the humoral response indicated that specific antibodies are directed against a few protein moieties. The fact that passive transfer of antibodies protected fish from experimental infection suggests that the basic mechanism of protection is antibody mediated. L. garvieae autovaccines developed for Italian trout farming were found to elicit a response similar to that of S. iniae. Despite the high virulence of L. garvieae (LD50 of 6 x 10(1) CFU/fish, compared with 3 x 10(4) CFU/fish of S. iniae), the protection against the experimentally induced disease lasted for five months under laboratory conditions, with survival rates of 80-90%. A single injection of the vaccine (0.1 ml/fish) resulted in specific antibody production detectable for six months. In the field, protection rates of 70-80% were obtained for a period of three months, in fish of 200-300 g reared at water temperatures of 18-21 degrees C.