Non-endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975–1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non-Salmonella gram-negative bacteremias. Salmonella was the single most frequent gram-negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non-lupus population. Presentation was characterized by fever (>103°F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.