To assess the impact of the human immunodeficiency virus epidemic on nontyphoidal Salmonella septicemia and to identify risk factors for this infection, national laboratory-based Salmonella surveillance data and AIDS case reports were analyzed. Among 25- to 49-year-old men in states with a high incidence of AIDS, the proportion of Salmonella isolates reported from blood increased from 2.8% in 1978–1982 to 14.2% in 1983–1987, with substantial increases for serotypes enteritidis and typhimurium. Of adolescents and adults reported with AIDS from September 1987 through March 1990, 337 (0.48%) had recurrent Salmonella septicemia, with higher proportions among those who resided in the Northeast (0.86%), had a history of intravenous drug use (0.79%), or were black (0.74%) or Hispanic (0.57%). These data suggest that the risk of Salmonella septicemia in persons with AIDS is affected by geographic prevalence of Salmonella species, host characteristics, and invasiveness of infecting strains