Cessation of cell proliferation in the transition zone is mediated by the canonical BMP-specific Smad pathway. Sections of P3 eyes were labeled with antibody to BrdU, and the labeling indices in the transition zone and the cortical fiber cell zone were determined. A significant increase in the BrdU-labeling index was seen in the transition zone and cortical fiber cells of lenses lacking the Co-Smad Smad4 (A, E) or the BMP-specific R-Smads Smad1 (B, F) and Smad5 (C, G). No abnormal proliferation was seen in the transition zone or cortical fiber cells of lenses lacking the non-BMP R-Smad Smad2 (D, H). *P < 0.05; ** P < 0.01; ****P < 0.0001.