Following an outbreak of foodborne gastroenteritis caused by Salmonella typhimurium, questionnaires were sent to affected individuals and then to the family physicians of any who experienced extra-enteric complications. Of 260 individuals infected with S typhimurium for whom adequate data were obtained, 19 patients developed joint disease (7.3%). All were men; the mean age ± SD was 39.3 ± 1.6 years. Among the 16 patients for whom this information was available, the interval from the onset of diarrhea to the onset of joint pain was <7 days in 7, 8–21 days in 2, and >21 days in 7. There was a significantly longer duration of diarrhea in those patients with joint disease (mean ± SEM 15.2 ± 2.6 days) than in those without complications (10.0 ± 1.1 days) (P < 0.01). The joint disease was monarticular in 3 patients and polyarticular in 16. The joints most commonly affected were the elbow (47%), wrist (47%), knee (42%), low back (32%), and shoulder (32%). Six of the 19 patients had at least 1 extraarticular feature: ocular (5 patients), mucosal (1 patient), urethral (2 patients), or cutaneous (1 patient). Of these 19 patients, 11 were located and agreed to HLA typing. Four were positive for HLA—B27, 6 were HLA—B7 positive, and 1 had HLA—Bw60. Of the 4 B27 positive patients, 3 were DR1 positive; of the 6 B7 positive patients, 5 were DR2 positive. A followup assessment 12.1 months after the acute infection revealed that of the 15 patients with arthritis (4 patients were lost to followup), 8 no longer had symptoms and 7 had persistent joint symptoms. Mucosal and urethral symptoms had resolved in all, and ocular symptoms had resolved in 90%. These findings highlight the interplay of microbe and major histocompatibility complex, a phenomenon that appears to be a precondition for the development of reactive arthritis.