Challenge studies with Mycobacterium marinum clearly demonstrate that a poor diet affects the progression and severity of mycobacteriosis in striped bass Morone saxatilis. Fish (n = 512 total, wt = 65 +/- 15 g) were inoculated intraperitoneally with 10(4) colony-forming units (CFU) g(-1) body weigth (BW) or a physiological saline solution (controls) and evaluated for 8 mo. Inoculated fish fed a low-ration diet (0.15% BW d(-1)) developed a severe, systemic infection characterized by a high bacterial load (>10(8) CFU g(-1) spleen) and poor granuloma formation, which commonly progressed to mortality by 6 wk. In contrast, inoculated fish fed an adequate ration diet (1% BW d(-1)) developed classic granulomatous inflammation of reduced severity and total body energy similar to that found in uninoculated controls (p > 0.05). After 4 wk, fish fed adequate rations maintained an equilibrium state throughout the study period, even though 10(6) CFU g(-1) spleen mycobacteria were consistently cultured. In a second study, reactivation of an acute inflammatory state was demonstrated by placing previously infected fish on reducing diets (0.073% BW d(-1)). In both studies, the energetic demand of this disease was only appreciable when associated with active, severe, inflammatory states. To our knowledge, this study is the first to demonstrate the interaction of diet and mycobacteriosis in fish.