The clinical course of 11 patients is reported: a newly-described species, Scedosporium inflatum, was isolated from each. Infections were primarily focally invasive and involved musculoskeletal tissues. All but one followed penetrating trauma, often minor, or surgery. Two cases, one fatal, occurred in immunosuppressed patients. In only one case was there presumptive hematogenous spread. In three cases colonization with S. inflatum could not reliably be distinguished from infection. In vitro susceptibility testing of isolates from all patients showed that all were resistant to amphotericin B, miconazole, and ketoconazole and most were resistant to fluconazole and itraconazole. The optimum management of S. inflatum infection is not apparent: Although several patients recovered without antifungal therapy, progressive unremitting infection occurred in an immunocompromised patient and in a previously healthy child despite aggressive antifungal chemotherapy and surgical debridement. © 1990 by The University of Chicago. All rights reserved.