Nest box use by gray squirrels (Sciurus carolinensis) and southern flying squirrels (Glaucomys volans) was studied in 2 isolated hardwood stands in the South Carolina Piedmont from December 1980 through December 1983. Over a 3-year period, an average of 94% of 100 boxes were used by squirrels. The number of squirrels occupying boxes increased (P < 0.001) over the 3-year period. Parturition dates and litter sizes were determined for 104 litters containing 283 squirrels. Two peaks of parturition occurred: 47% of the litters were born during January to March, and 46% were born during August to October. Differences in nest box use by squirrels between study areas, box use by other species, and effects of nest boxes on estimated squirrel densities are discussed.