Salmonellosis is a major cause of illness in the United States. To highlight recent trends, data for 1987-1997 from the National Salmonella Surveillance System were analyzed. A total of 441,863 Salmonella isolates were reported, with the highest age-specific rate among infants (159/100,000 infants at 2 months). Annual isolation rates decreased from 19 to 13/100,000 persons; however, trends varied by serotype. The isolation rate of Salmonella serotype Enteritidis increased until 1996, whereas declines were noted in Salmonella serotypes Hadar and Heidelberg. Overall, serotypes that increased in frequency were significantly more likely than those that decreased to be associated with reptiles (P=.008). Salmonella infections continue to be an important cause of illness, especially among infants. Recent declines in food-associated serotypes may reflect changes in the meat, poultry, and egg industries that preceded or anticipated the 1996 implementation of pathogen-reduction programs. Additional educational efforts are needed to control the emergence of reptile-associated salmonellosis.