One of the goals of the Florida panther (Puma concolor coryi) recovery plan is to expand panther range north of the Caloosahatchee River in central Florida. Our objective was to evaluate the potential of that region to support panthers. We used a geographic information system and the Mahalanobis distance statistic to develop a habitat model based on landscape characteristics associated with panther home ranges. We used cross-validation and an independent telemetry data set to test the habitat model. We also conducted a least-cost path analysis to identify potential habitat linkages and to provide a relative measure of connectivity among habitat patches. Variables in our model were paved road density, major highways, human population density, percentage of the area permanently or semipermanently flooded, and percentage of the area in natural land cover. Our model clearly identified habitat typical of that found within panther home ranges based on model testing with recent telemetry data. We identified 4 potential translocation sites that may support a total of approximately 36 panthers. Although we identified potential habitat linkages, our least-cost path analyses highlighted the extreme isolation of panther habitat in portions of the study area. Human intervention will likely be required if the goal is to establish female panthers north of the Caloosahatchee in the near term.