In vitro studies have shown that rifampicin is an effective antibiotic for mycobacteria infections. Two species of tropical fish, the Firemouth Cichild Cichlasoma meeki and the Congo Tetra Phenacogrammus interruptus, were used to determine whether oral application of rifampicin might serve as an effective treatment for mycobacteriosis in tropical fish. Fish of the two species were infected with M. marinum under controlled conditions. Six or twelve weeks after infection, treatment was begun with medicated fish food containing rifampicin in combination with tetracyclin. Histological examination of epithelial cell granuloma in the anterior and posterior kidneys, as well as in liver and spleen, showed that antibiotic treatment could somewhat reduce the intensity of, but could not successfully eliminate infection. In addition, after treatment, acid-resistant rods could still be isolated from histological samples and M. marinum could be cultured from organ samples.