The clinical features, essential laboratory findings, management, and outcome of all 23 cases of septic arthritis caused by different serogroups of beta-hemolytic streptococcus (BHS) seen at the Stanford Medical Center, Stanford, CA, from July 1, 1985, through October 31, 1996, were reviewed and compared to those found in the literature. Group A streptococci (GAS) accounted for 9 (40%) of our cases; group B (GBS), for 7 (30%); and Group G (GGS), for 7 (30%). No cases were caused by Group C (GCS) or F (GFS) during this period. During the same period, GAS accounted for 66 (33%) of 200 cases of bacteremia due to BHS, GBS, for 98 (49%); GCS, for 12 (6%); GFS, for 4 (2%); and GGS, for 20 (10%). A review of potential risk factors revealed that, with the exception of GGS, male and female patients were almost equally distributed among each of the serogroups. Patients aged 50 years and older comprised 56%-77% of each group. Associated conditions and risk factors were present among most patients (19/23, 83%); autoimmune diseases and a chronic skin wound or trauma were notably present among patients with GAS, while diabetes mellitus and malignancy were more common among patients with GBS. Infected prosthetic implants were present in 7 patients, including 4/7 patients with GGS. All patients had positive cultures of synovial fluid, and 11/23 (49%) had positive blood cultures (GAS, 5/9; GBS, 6/7; and GGS, 0/7). The clinical presentation and hospital course of patients infected with the different serogroups varied. Patients infected with GAS had the most severe disease and those with GGS the least severe. Necrotizing fascitis, shock, DIC, and admission to the intensive care unit were found only among patients infected with GAS. Despite aggressive management with antimicrobial therapy and surgery, 4/23 patients died (3 patients with GAS; 1 with GBS). The isolates from our patients were not available for study; investigations by others of the biology of BHS suggest that the production of 1 or more of the streptococcal pyrogenic exotoxins by isolates of GAS may account for the differences in the severity of disease among our patients with septic arthritis caused by different serogroups of BHS. Although septic arthritis due to BHS is uncommon, such patients provide a valuable model to study features of the host-parasite interaction that may contribute to the observed differences in severity of disease.