Vein grafts become thicker as they adapt to arterial circulation, and in large measure this is the consequence of cellular hyperplasia. The kinetics of smooth muscle cell (SMC) and endothelial cell (EC) replication were evaluated in rabbit jugular vein segments transplanted into the carotid arterial circulation to define the role of cell proliferation in this process, and these data were correlated with dimensional changes in grafts from 1 hour to 24 weeks after implantation. At 1 hour most of the perianastomotic endothelium was denuded, as were occasional cells in the graft away from the anastomosis. EC replication (thymidine labeling index) in the center of the graft increased 400 times during the first week and produced an intact endothelial surface by 2 weeks. The EC thymidine index then fell progressively to quiescent pretransplant levels by the twelfth week. SMC replication was maximal at 1 week after grafting and returned to near quiescent levels at 12 and 24 weeks. Graft wall thickness and cross-sectional area reached a maximum at 12 weeks and then remained constant. Deoxyribonucleic acid content exhibited a thirty-five-fold increase in the first 4 weeks, then did not change. Likewise, SMC mass did not increase after 4 weeks. Further increase in cross-sectional wall area between 4 and 12 weeks was accounted for by accumulation of connective tissue. The final ratio of luminal radius to wall thickness decreased to a level equal to that of normal artery. Since blood pressure did not change over the period of the study, this observation supports a possible regulatory role for wall tangential stress in the modification of vein graft structure after transplantation into the arterial circulation.