Invasive Salmonella infections are severe and can be life threatening. We analyzed population-based data collected during 1996-1999 by the Foodborne Diseases Active Surveillance Network (FoodNet), to determine the incidences, infecting serotypes, and outcomes of invasive Salmonella infection. We found that the mean annual incidence of invasive salmonellosis was 0.9 cases/100,000 population and was highest among infants (7.8 cases/100,000). The incidence was higher among men than women (1.2 vs. 0.7 cases/100,000; P<.001) and higher among blacks, Asians, and Hispanics than among whites (2.5, 2.0, and 1.3 cases/100,000 population, respectively, vs. 0.4 cases/100,000; all P<.001). Seventy-four percent of cases were caused by 8 Salmonella serotypes: Typhimurium, Typhi, Enteritidis, Heidelberg, Dublin, Paratyphi A, Choleraesuis, and Schwarzengrund. Of 540 persons with invasive infection, 386 (71%) were hospitalized and 29 (5%) died; 13 (45%) of the deaths were among persons aged > or =60 years. Invasive Salmonella infections are a substantial health problem in the United States and contribute to hospitalizations and deaths.