Fresh produce increasingly is recognized as an important source of salmonellosis in the United States. In December 1999, the Centers for Disease Control and Prevention detected a nationwide increase in Salmonella serotype Newport (SN) infections that had occurred during the previous month. SN isolates recovered from patients in this cluster had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns (which identified the outbreak strain), suggesting a common source. Seventy-eight patients from 13 states were infected with the outbreak strain. Fifteen patients were hospitalized; 2 died. Among 28 patients enrolled in the matched case-control study, 14 (50%) reported they ate mangoes in the 5 days before illness onset, compared with 4 (10%) of the control subjects during the same period (matched odds ratio, 21.6; 95% confidence interval, 3.53- infinity; P=.0001). Traceback of the implicated mangoes led to a single Brazilian farm, where we identified hot water treatment as a possible point of contamination; this is a relatively new process to prevent importation of an agricultural pest, the Mediterranean fruit fly. This is the first reported outbreak of salmonellosis implicating mangoes. PFGE was critical to the timely recognition of this nationwide outbreak. This outbreak highlights the potential global health impact of foodborne diseases and newly implemented food processes.