Arvicoline rodents serve as model organisms for investigating the intricacies of ecological/evolutionary feedbacks that characterize multiannual fluctuations in abundance. A population of California voles (Microtus californicus) in central California was followed for 3.5 years using 4 small grids located 50 m apart. Blood samples were scored for 4 polymorphic allozyme loci by starch gel electrophoresis. These were carefully chosen for their potential to reveal details of genetic structuring among demes. A low density of voles developed into a peak followed by a rapid decline to low density. Heterozygosity averaged 20.2% (n = 709) with loci-specific shifts associated with density, season, and cyclic phase. Statistically significant heterogeneity in genotypic and allelic frequencies among the grids was found for 3 of the loci. Pairwise comparisons among the grids for each locus separately (n = 24) yielded 11 significantly disparate pairs for genotypic frequencies and 10 for alleles. Significant correlations with cyclic phase were found at 1 locus (leucine aminopeptidase). Spatial differentiation among grid pairs (F_ST) ranged up to a 12-fold difference. F_ST values stratified by cyclic phase showed the highest levels in the pre-high phase and the lowest in the postpeak. A “founder/flush” model with sequential phases of semi-isolated low-density demes followed by panmixia at high densities, and then a density crash is supported. This pattern is postulated to facilitate adaptive evolution.