Salmonella bacteremia is being identified with increasing frequency in persons infected with the human immunodeficiency virus. Salmonellosis may occur in patients with an established diagnosis of acquired immunodeficiency syndrome (AIDS), or it may be the first manifestation of this disorder. In patients with AIDS, salmonellosis is characterized by recurrent bacteremia despite treatment and a relative paucity of gastrointestinal manifestations. Treatment regimens may be limited by antimicrobial resistance, poor penetration of antibiotics into phagocytes, and drug intolerance; optimal therapy remains to be established. Possible mechanisms to account for this increased frequency and severity of salmonellosis include altered cell-mediated immunity, hemolysis, prior use of antibiotics, and increased exposure to the pathogen. Salmonellae should be considered among the pathogens associated with human immunodeficiency virus infection.