In the present study, 8 patients with soft tissue infection due to Mycobacterium marinum are described, and contemporary data on treatment are reviewed. Six patients had positive cultures, all patients had cutaneous exposure to fish tanks, 7 had sporotrichoid lesions, and 2 had deep infection. All 7 tested patients had tuberculin skin test reactions > or =10 mm. Six patients with disease limited to the skin were successfully treated with 2-drug combination therapy, including clarithromycin, ethambutol, and rifampin. Optimal treatment should include 2 drugs for 1-2 months after resolution of lesions, typically 3-4 months in total. Deeper infections may require more prolonged treatment and surgical debridement. Positive tuberculin reactions may be due to infection with M. marinum. Persons with open skin lesions or immunosuppression should avoid cutaneous contact with fish tanks.