A sample of the Khmer population from Cambodia has been examined for 30 single-gene characters (10 blood groups and 20 serum and red cell systems). A locus-by-locus comparison suggests that the Khmers differ significantly in several systems from the populations of Eastern India and China. There is remarkable heterogeneity among their geographical neighbors. To elucidate the genetic relationship of the Khmer, genetic data were collected from various published and unpublished sources, and different multivariate analyses were performed. The analyses show that the Khmers definitely show closer affinity for the neighboring populations of Thailand and Malaysia. The Chinese population not only shows a close relationship to the Khmers, but also consistently stays close to the populations of the Southeast Asian peninsula. The present-day Khmers are genetically distant from the population of Eastern India, but the analyses do not totally exclude gene flow from Eastern India. It is, therefore, concluded that the original gene pool of Khmers may have derived from China, being modified by mixing with the local and Indian migrant populations. © 1994 Wiley-Liss, Inc.