During a four-year period, twenty-one patients were found to have melioidosis of the musculoskeletal system caused by Pseudomonas pseudomallei. The melioidotic patients were matched with thirty-nine patients who had a musculoskeletal infection due to some other organism, and the two groups were compared with regard to the presence of concurrent disease. The indirect hemagglutination test for melioidosis was positive for all of the melioidotic patients; in thirteen, cultures also were positive. For the patients who did not have melioidosis, the diagnosis was made on the basis of positive cultures of other organisms or histological sections. In most of the non-melioidotic patients, the infection was due to Staphylococcus aureus (twenty-four patients) or to Mycobacterium tuberculosis (twelve patients). The most common concurrent diseases in the melioidotic patients were diabetes and thalassemia. The odds that melioidosis was the cause of the infection in a patient who had a concurrent disease were twelve to one. All melioidotic patients were managed with operative debridement and a combination of drugs--usually, trimethoprim and sulfamethoxazole, doxycycline, and kanamycin or chloramphenicol--for six months. The mean duration of follow-up was one and one-half years. Of the twenty-one patients, eighteen had an excellent or good result in terms of motion of the joint and absence of relapse.