On September 4, 2008, the Philadelphia Department of Public Health (PDPH) and the Pennsylvania Department of Health (PADOH) notified CDC of an outbreak of possible turtle-associated human Salmonella Typhimurium infections detected by identifying strains with similar pulsed-field gel electrophoresis (PFGE) patterns in PulseNet. Turtles and other reptiles have long been recognized as sources of human Salmonella infections, and the sale or distribution of small turtles (those with carapace lengths <4 inches) has been prohibited in the United States since 1975. CDC and state and local health departments conducted a multistate investigation during September-November 2008. This report summarizes the results of that investigation, which identified 135 cases in 25 states and the District of Columbia; 45% were in children aged <or=5 years. Among 70 patients with primary infection, 37% reported turtle exposure, of which 81% was to small turtles most commonly purchased from street vendors. A matched case-control study showed a significant association between illness and exposure to turtles (matched odds ratio [mOR] = 16.5). Increasing enforcement of existing local, state, and federal regulations against the sale of small turtles, increasing penalties for illegal sales, and enacting more state and local laws regulating the sale of small turtles (e.g., requiring Salmonella awareness education at the point-of-sale), could augment federal prevention efforts.