Abstract Circadian periodicity of DNA synthesis (S) phase and mitosis over a complete 12-hour light/12-hour dark cycle was studied in rat molar periodontal ligament (PDL) with 3H-thymidin autoradiography. Maximum percent labeled cells was at 10 a.m. in all regions, and mean labeling (24-hour average) was 1.44, 0.93, and 1.46 percent for the crest, midroot, and apical areas of the PDL, respectively. Maximum percent mitotic figures were also at 10 a.m. in all areas studied, and the mean number of mitoses averaged over 24 hours was 0.19, 0.12, and 0.14, respectively for crest, midroot, and apical areas. Ratios of mean labeling and mitotic indices were 7.58, 7.75, and 10.43 from crest to apex. Duration of mitosis and S phase were estimated at 1.2 and 9 hours, respectively. Analysis of data suggested that stress/strain within the PDL, associated with masticatory function, has a regional influence on duration of S phase, mitotic rate, and percentage of cells in the S phase. These results help define an in vivo experimental model for assessing the PDL cellular response to biomechanically defined force systems. Clinical implications are discussed.