House mice have been isolated on the small Welsh island of Skokholm since the 1890s, when the island was colonized by a few animals inadvertently brought over from the nearby mainland in sacks. This paper describes a study (by starch gel electrophoresis) of variants at six gene loci in samples from the island population collected at the beginning and end of breeding in two consecutive years. Four mainland mouse populations were sampled for comparison. The Skokholm mice were polymorphic at all six loci, and were segregating for fourteen of the fifteen alleles found in the mainland samples. Three of the six loci on Skokholm indicated the action of natural selection: two showed an increase over the number of heterozygotes expected on the Hardy-Weinberg equilibrium during one season (winter in one case, summer in the other) and a decrease in this excess at another time of year, while the third showed directed selection against mice carrying a particular allele. These changes in allele and genotype frequencies occurred during the first year of the study and were repeated in the second year. Variants at the other three loci indicated the influence of the social structure of the mice on allele distribution, showing that the population was not behaving as a panmictic unit. These results have to be interpreted in terms of the ecology and population dynamics of the island mice. The population size varies considerably: during the winter there is no successful breeding and a mortality of 50 to 90%, the number dying depending on the mean temperature in early spring; in the summer the population increases tenfold (much less than the increase predicted from knowledge of litter sizes and breeding rates: there must be considerable juvenile mortality). Despite the poverty of genic variation that must have existed in the early stages of colonization on Skokholm, natural selection has acted to increase the variation to a level not very different from that on the mainland.