Severe systemic mycobacteriosis without typical granuloma formation was diagnosed in a group of six mature, captive, striated frogfish Antennarius striatus approximately 5 mo after fish originating from Brazil were purchased by Mote Marine Laboratory Aquarium. Beginning 1 mo after spawning, over a period of 9 mo, individuals began to show a variety of signs including egg retention, ocular opacity, poor buoyancy control, ascites with coelomic distension, skin lesions, and anorexia. Two fish died, and four were euthanatized. At necropsy, raised pigmented skin nodules; pale pink gills; and pale yellow or tan, fatty livers were noted. A systemic fungal infection was diagnosed histopathologically in one female, and the remaining fish had severe, systemic, histiocytic inflammation and necrosis. Although large numbers of acid-fast bacterial rods were identified in each fish, no bacteria were cultured aerobically from skin, kidney, spleen, liver, or brain. Mycobacterium marinum was cultured from the liver of the last fish that was euthanatized after it became moribund and failed to respond to symptomatic treatment.