The United States and Mexico share an international boundary similar to 3000 km long. This border separates 2 nations with great differences in health status. The objective of this study was to assess morbidity due to infectious diseases in the US region bordering Mexico. The incidence between 1990 and 1998 of 22 nationally notifiable infectious diseases was compared between border and nonborder regions, Disease rates, reflected as rate ratios, were higher in the border region for botulism, brucellosis, diphtheria, hepatitis A, measles, mumps, rabies, rubella, salmonellosis, and shigellosis than in either of 2 nonborder comparison regions. These data indicate that incidence rates for a variety of infectious diseases of public health importance are significantly higher in the United States along the Mexican border than in nonborder regions, These results suggest that an inadequate public health infrastructure may contribute to excess morbidity due to infectious diseases in the border region.