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The relative paucity of information about systemic nontyphoidal Salmonella (NTS) infection in infants without an underlying disease prompted this study.Infants without an underlying disease, who had positive cultures for NTS from their normally sterile sites during 1978 through 1998, were included. Their medical records were reviewed.The study included 75 eligible infants; 68 (91%) had positive blood cultures. The spectrum of disease included transient bacteremia (5), bacteremia without localized infection (37), bone and joint infection (5) and meningitis (28); 53 and 88% of infants were ≤3 and ≤6 months old, respectively. All infants with localized infection were ≤7 months old, and infants with meningitis were 3.35 ± 1.87 (mean ± sd) months old. In bacteremic infants risks for localized infection and meningitis were 30 and 24%, respectively. Abnormal neurologic findings were the only predictor for meningitis. Relapse of meningitis occurred in two infants despite treatment with cefotaxime for 4 and 6 weeks. Severe neurologic deficit occurred in 21% of infants with meningitis. Of 11 infants with meningitis who received early treatment at this tertiary care center, 1 died but none had severe neurologic deficits; whereas of 17 referred cases, 2 died and 6 had severe neurologic abnormalities. No death occurred in infants without meningitis.Systemic NTS infection in normal infants has a variable disease spectrum. Infants 0 to 6 months of age are at high risk for localized infection, especially meningitis.