Understanding how patchy landscapes affect the distribution and abundance of species is a central issue in applied ecology. We examined the effects of landscape structure on the distribution of the Florida scrub lizard (Sceloporus woodi) in naturally fragmented habitat. Scrub lizards were absent from 89 of 132 patches, and their distribution was explained in multifactor models by two landscape variables: patch size and patch isolation. Mark-recapture studies of S. woodi and experimental displacement trials indicate that this species exhibits low vagility within a patch and that movement through dense habitat, which often characterizes the landscape matrix, is restricted. Poor dispersal ability relative to the degree of isolation of patches in this landscape may account for large gaps in its distribution. To examine the applicability of the scrub lizard model to other species, we applied the model to a sympatric lizard, the six-lined racerunner (Cnemidophorus sexlineatus), which is similar in body size, food habits, and habitat requirements. The racerunner was more widely distributed than the Florida scrub lizard within our scrub landscape, and the model failed to predict its distribution. This differing response to landscape structure by a similar species is likely due to the greater dispersal ability of C. sexlineatus. Our results, and similar studies of other scrub organisms, indicate that each species may have a unique response to habitat fragmentation. The design and management of effective preserves for Florida scrub will require a multiscaled, multispecies approach that reflects the differences in the dispersal abilities, area requirements, and habitat preferences of the species to be preserved.