The liver is commonly involved in patients with typhoid fever. However, severe hepatic derangement simulating acute viral hepatitis is rare. Our aim was to characterize the clinical picture, biochemical features, and prognosis of Salmonella hepatitis. Retrospective case-control analysis of medical records included 27 patients with Salmonella hepatitis and 27 inpatients with acute viral hepatitis from 1973 to 1993. Travel history, clinical picture, a standard battery of 18 biochemical tests, complete blood counts, disease complications, duration of hospital admission, and final outcome were analyzed. Eleven patients with Salmonella hepatitis (40%) travelled abroad within 1 month of illness. A greater proportion of Salmonella hepatitis patients developed fever > 104 degrees (44% vs. 4%, respectively; P < .0001), and had relative bradycardia (42% vs. 4%, respectively; P < .002) than viral hepatitis patients. Salmonella hepatitis was associated with lower peak serum alanine transaminase (ALT), aspartate transaminase, and higher peak serum alkaline phosphatase (296 vs. 3,234 U/L, 535 vs. 2,844 U/L, and 500 vs. 228 U/dL, respectively; P < .0001, <.0003, and <.004). The admission ALT/lactic dehydrogenase (LDH) ratio, when levels of both enzymes were expressed as multiples of upper limit of normal value for each, was significantly lower in Salmonella hepatitis. All Salmonella hepatitis cases had a ratio < 4, and all viral hepatitis cases had a ratio > 5, P < .0001. Left shift of white blood cells was more common in Salmonella hepatitis (83% vs. 37%; P < .004). Patients with Salmonella hepatitis had a longer hospitalization (14.8 vs. 6.5 days, respectively; P < .0001). All 54 patients survived their illness. The clinical picture of Salmonella hepatitis is frequently indistinguishable from viral hepatitis. The admission ALT/LDH ratio is the best discriminator between both entities. Other clues that raise the possibility of Salmonella hepatitis include high fever, relative bradycardia, and left shift of WBCs. Despite long hospitalization, Salmonella hepatitis responds to proper antibiotic therapy and has an excellent prognosis.