Calomys musculinus is the natural reservoir of Junin virus, the etiological agent of Argentine hemorrhagic fever. In this paper we measure the effective size of 2 populations of the rodent over a 2-year period. Twenty enzyme-coding loci were analyzed using vertical starch gel electrophoresis. Effective population sizes (N_es) were estimated by the pseudolikelihood method in 2 populations 280 km apart in central Argentina. Both populations experienced marked seasonal changes in relative density and in N_e (between 19.8 and infinity). Changes in percentage of polymorphic loci and mean number of alleles per locus were statistically significant and were roughly correlated with density and N_e. Observed changes in heterozygosity, in contrast, were not significant. After low-density periods, mixing of surviving individuals coming from different demes may play an important role in the maintenance of variability and recovery of N_e in populations of C. musculinus.