Amphotericin B is recommended for the treatment of systemic infection caused by Sporothrix schenckii. However, this agent is toxic, its use is frequently followed by relapse, and some isolates of S. schenckii are resistant. Recent studies suggest that newer azole compounds, such as itraconazole, are effective in cutaneous and lymphocutaneous sporotrichosis, but data on their efficacy in systemic infections are scarce. We used itraconazole in the sequential treatment of six patients with systemic sporotrichosis: three with bone and joint disease and three with disseminated infection manifested by subcutaneous nodules. In all six cases, symptoms and signs of infection improved, with resolution of subcutaneous nodules, normalization of imaging studies, cessation of wound drainage, and return of joint mobility and function. No toxicity was noted. One patient with disseminated infection had a relapse while receiving 100 mg of itraconazole daily. The average duration of follow-up was 18 months. Thus itraconazole appears promising for the treatment of systemic sporotrichosis. A dose of at least 200 mg/d appears to be needed to prevent relapse.