Tijuana, Mexico, just south of San Diego, California, is located by the busiest land border crossing in the world. Although UNAIDS considers Mexico to be a country of "low prevalence, high risk," recent surveillance data among sentinel populations in Tijuana suggests HIV prevalence is increasing. The aim of this study was to estimate the number of men and women aged 15 to 49 years infected with HIV in Tijuana. Gender and age-specific estimates of the Tijuana population were obtained from the 2000 Mexican census. Population and HIV prevalence estimates for at-risk groups were obtained from published reports, community based studies, and data from the Centro Nacional para la Prevención y Control del VIH/SIDA (CENSIDA). Age-specific fertility rates for Mexico were used to derive the number of low and high-risk pregnant women. Numbers of HIV-positive men and women were estimated for each at-risk group and then aggregated. A high growth scenario based on current HIV prevalence and a conservative, low growth estimate were determined. A total of 686,600 men and women in Tijuana were aged 15 to 49 years at the time of the 2000 census. Considering both scenarios, the number of infected persons ranged from 1,803 to 5,472 (HIV prevalence: 0.26 to 0.80%). The majority of these persons were men (>70%). The largest number of infected persons were MSM (N = 1,146 to 3,300) and IDUs (N = 147 to 650). Our data suggest that up to one in every 125 persons aged 15-49 years in Tijuana is HIV-infected. Interventions to reduce ongoing spread of HIV are urgently needed.