In a retrospective study at Hospital del Niño in Panama City, Panama, 577 neonates with culture-proved sepsis and/or meningitis were identified during an 18-year period (1975 to 1992). Overall there was an incidence of 3.5 cases/1000 live births. Three hundred thirty-three patients (58%) were of low birth weight (< 2500 g) and 260 (45%) were premature. Gram-negative bacilli, particularly species of Klebsiella and Escherichia coli, were responsible for 61% of infections, whereas Gram-positive isolates (especially staphylococci) and Candida strains accounted for 37 and 2%, respectively. The patterns of predominance among bacterial pathogens, however, changed during the period of study. In the later years of this study the frequency of Gram-negative bacteria declined whereas those of staphylococci and Candida increased. Likewise systemic infections caused by Group B Streptococcus organisms appeared recently. The case-fatality rate was 32%. Mortality was greater in infants with early onset sepsis than in those with late infections (44% vs. 22%, P < 0.0001; odds ratio, 2.8; 95% confidence interval, 1.9 to 4.1) and lesser in neonates infected by coagulase-negative staphylococci than in those infected by any other pathogen (12 vs. 39%, P < 0.001; odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4). These findings provide guidelines for the selection of empiric antimicrobial agents in our country and possibly in other Latin American countries and suggest that a continued thorough epidemiologic evaluation is needed to anticipate bacteriologic changes over time.