Phenotypes and gene frequencies of 24 genetic markers (9 blood groups, 11 red cell enzymes, and 4 serum proteins) were investigated in 5 occupational caste groups (Brahmin, Khatri, Vaish, Kayastha, and scheduled castes) and 1 religious group of Muslims in Uttar Pradesh, India. This is the first extensive genetic study in Uttar Pradesh that establishes the range of genetic variation in different endogamous groups. The extent of genetic variation among different occupational caste groups is low, and only two genetic systems (C3 and ACP) showed heterogeneity. The genetic affinity analysis showed an unexpected close affinity of scheduled castes with the Khatri. This observation warrants further analysis of these groups, but the present results may be a chance finding resulting from the nature of the samples, which represent individuals from vastly different regions of Uttar Pradesh. The affinity of the Muslim group with other caste groups suggests that the samples may include descendants of converts from the seventeenth century who are still at an early stage of differentiation. The FST estimate for the populations is 0.009, which is close to other estimates reported from north and northwest India. The overall mean FIS value is 0.066, and for each locus the FIS estimate is considerably higher than the FST estimate, suggesting that the infrastructure of the populations is influenced by nonrandom mating (inbreeding). There is no evidence of any disruptive selection, but the allele frequency of each caste group of Uttar Pradesh must be affected by its large population size, which, because of chance migration of individuals with different gene frequencies, would accentuate genetic differences.