Lake trout Salvelinus namaycush is a slow-growing, late-maturing, cold-water-adapted species whose native distribution is described by the glaciated regions of North America. Southwestern Alaska, the western limit of the species range, has undergone repeated episodes of glacial advance and retreat. In this study, lake trout were sampled from 15 lakes in six drainages on or near Togiak National Wildlife Refuge (TNWR) in southwestern Alaska. Data from 14 microsatellite loci were used to test for genetic evidence that lake trout survived the most recent glacial advance in a local refugium, and to test the effect of habitat size, elevation, and drainage on within- and among-population variation. We could not infer that unglaciated lakes within the TNWR served as a refugium during the most recent glacial maximum. In a neighbor-joining tree, populations largely clustered by drainage, suggesting a single founding source for each drainage. An exception occurred in the Nushagak and Kuskokwim rivers, where evidence for stream capture was detected. Among-population variation, as measured by F ST, was 0.35; pairwise F ST within drainages ranged from 0.05 to 0.47, indicative of low gene flow, even within drainages, though individual-based analysis detected movement of lake trout among lakes within the Kanektok, Goodnews, and Nushagak rivers. Lake surface area was positively associated with allele richness, and negatively associated with F IS, indicating that smaller lakes in the TNWR harbor less genetic diversity and may have more limited adaptive potential.