Blood samples were collected from healthy subjects, aged 9 months-29 years in urban and rural communities from 4 distinct regions in Thailand, to determine the seroprevalence rate of varicella-zoster virus (VZV) antibody and its relationship with demographic, climatic, and socioeconomic factors. The overall seroprevalence rate was 52.8% and increased from 15.5% in the 9-month to 4-year-old group to 75.9% in the 20-29 year-olds. The age-adjusted seroprevalence was significantly higher in the cooler than in the warmer regions. In the warmer regions only, the age-specific seroprevalence was significantly higher in the urban population than in the rural population. In Thailand, climate is the main determinant of VZV seroprevalence. The delayed onset of natural immunity is more marked in warmer climate areas. Population density is a secondary determinant; in the warmer areas, the pattern of adolescent and adult susceptibility was greater in rural than in urban areas.