Five cases of human infection with Scedosporium prolificans are described. There were two groups of patients. In group one, two were immunocompetent males with localized bone and joint infections, a man with post-traumatic septic arthritis, responded to surgical treatment alone and a boy with post-traumatic septic arthritis, appeared to respond to treatment with oral fluconazole, without surgery. The second group consisted of three immunocompromised patients. S. prolificans was isolated at autopsy from the lungs of one patient with acute leukaemia, and from the lungs, liver, and kidneys of another. Nosocomial S. prolificans infection of a synthetic vascular graft occurred in the third patient with end-stage renal failure on corticosteroid therapy for idiopathic hypereosinophilia. His infection failed to respond to combinations of surgery, fluconazole and itraconazole. All isolates of S. prolificans were resistant in vitro to antifungal drugs, including the first case, which responded clinically to fluconazole.