SUMMARYA population of house mice, Mus musculus domesticus, from the village of Migiondo was found to be genetically distinct from nearby populations in Upper Valtellina (Italian Alps). At the supernatant malic enzyme locus, Mod1, the only alleles found in Migiondo (c and n2) were virtually absent from the other populations in the valley, which were characterized by allele a. The extraordinary genetic distinctiveness of the Migiondo population is apparently the result of genetic drift, perhaps coupled with a founder event, and attests to the existence of nearly impenetrable geographic barriers around the village isolating it from other settlements only a few hundred metres away. The Mod1 features of the house mice in Migiondo are reminiscent of the characteristics of house mice on maritime islands. The genetic confirmation of the geographic isolation of Migiondo is of interest because there is evidence that this village may have been the site of recent speciation and extinction events. The data are also of significance given the phenomenal chromosomal variation in house mice from the vicinity of the Alps. It has frequently been proposed that genetic drift\founder events are of importance in the fixation of chromosomal rearrangements ; this study provides the first direct evidence for their occurrence in alpine mouse populations.