Apoptosis is a key phenomenon in the regulation of the life span of odontoblasts, which are responsible for dentin matrix production of the teeth. The mechanism controlling odontoblasts loss in developing, normal, and injured human teeth is largely unknown. A possible correlation between apoptosis and dental pulp volume reduction was examined. Histomorphometric analysis was performed on intact 10 to 14 year-old premolars to follow dentin deposition and evaluate the total number of odontoblasts. Apoptosis in growing healthy teeth as well as in mature irritated human teeth was determined using a modified TUNEL technique and an anti-caspase-3 antibody. In intact growing teeth, the sequential rearrangement of odontoblasts into a multi-layer structure during tooth crown formation was correlated with an apoptotic wave that leads to the massive elimination of odontoblasts. These data suggest that apoptosis, coincident with dentin deposition changes, plays a role in tooth maturation and homeostasis. Massive apoptotic events were observed after dentin irritation. In carious and injured teeth, apoptosis was detected in cells surrounding the lesion sites, as well as in mono-nucleated cells nearby the injury. These results indicate that apoptosis is a part of the mechanism that regulate human dental pulp chamber remodeling during tooth development and pathology.