Sixty-eight patients who had had 159 replacement arthroplasties of more than one major joint between 1975 and 1984 and who had had an infection after at least one of these procedures were identified in a retrospective review. Subsequent infection in another total joint replacement was documented in ten of these patients. The risk of development of an infection about another total joint replacement after an infection had occurred about one total joint replacement in a patient who had had more than one arthroplasty was 18 per cent, according to the survivorship-analysis method of Kaplan and Meier. Many variables that were previously thought to increase the risk of infection, such as rheumatoid arthritis, older age of the patient, previous operations, and the use of corticosteroids or immunosuppressive agents, or both, were not found to increase the risk of a subsequent infection in patients who had had more than one arthroplasty with infection of one of the arthroplasties. The recent occurrence of a major systemic infection did increase the risk of infection about the other total joint replacements. Eight of the ten subsequent joint infections were due to the same causative organism as the index infection about a total joint replacement and occurred within the first year after the index infection. The initial treatment of the index infection included specific parenteral antimicrobial therapy combined with débridement and excisional arthroplasty in forty patients, removal of the components and arthrodesis in three patients, and débridement with retention of the prosthesis in twenty-five patients.(ABSTRACT TRUNCATED AT 250 WORDS)