The basic concept of herd immunity is directly applicable only under very special conditions. The agents of disease must be restricted to a single host species within which transmission occurs by relatively direct contact, and infection induces solid immunity. Also outbreaks must occur only in randomly mixing populations. In free-living populations, susceptibles are not distributed homogeneously but tend to cluster in subgroups defined by age and by such factors as ethnicity and socioeconomic status. The requisite for occurrence of epidemics, namely a large enough number of susceptibles in frequent contact with each other, exists in virtually all large populations, regardless of the total proportion of the population that is immune. Experience with measles illustrates these conditions. Total prevalence of immunity of greater than or equal to 90% in developing countries does not prevent annual epidemics among the susceptibles, most of whom are children younger than three years of age. Where vaccination is widely practiced, as in the United States since 1962, measles has continued to occur in poorly immunized subgroups that are characterized by low educational level and economic status, very young age, or religious beliefs forbidding acceptance of vaccine. Ultimate success of a systematic immunization program requires knowledge of distribution of susceptibles by age and subgroup and maximal effort to reduce the concentration of susceptibles throughout the community rather than aiming to reach any specific proportion of the overall population.