Surprisingly few studies have empirically compared genetic variation between central and peripheral populations of vertebrates, even though such populations are considered very important to evolutionary theories of anagenetic and cladogenetic change. This study assesses levels of microsatellite variability within and between populations of eastern collared lizards (Crotaphytus collaris collaris) sampled in three regions: the central part of its range and at the northeastern periphery in the southwestern and northeastern Ozarks. As expected, central populations possessed significantly higher within-population variability than peripheral populations, whereas the two peripheral subregions did not differ significantly from one another. Estimates of subdivision (F_st) differed significantly among all three regions in the following order: central < southwestern Ozark region < northeastern Ozark region. Estimates of subdivision between specially sampled populations separated by no more than 10 km indicated effective panmixia at the local level in the central region, historically high rates of localized dispersal in the southwestern Ozarks with recently imposed isolation and dominance of drift at all spatial scales in the northeastern Ozarks. These differences in regional population structure are consistent with regional differences in time of occupation by collared lizards, time and duration of forestation and latitudinal effects.