Objective: The aim of this study was to investigate the structure and mechanism of apoptosis in placentas with maternal hypothyroidism. Material and Methods: Seven normal and eight hypothyroidic mothers were selected. Tissues were prepared for histochemistry, immunohistochemistry and TUNEL assay for detection of apoptosis and structural changes. Results: Increased TUNEL-positive staining in the cytotrophoblast, syncytiotrophoblast and mesenchymal cells was shown in the placentas of the hypothyroid group in comparison to the control group. In the control group, positive immunostaining for Caspase-3 was moderate in the syncytiotrophoblast cells, while it was mild in the cytotrophoblast cells and it was negative in the mesenchymal cells. Immunostaining for Bcl-2 was moderate in the syncytiotrophoblast, cytotrophoblast and mesenchymal cells. Bax immunostaining was negative in the cytotrophoblast and mesenchymal cells, while immunostaining was mild in the syncytiotrophoblast. In the hypothyroid group, Caspase-3 immunostaining was strong in the syncytiotrophoblast, cytotrophoblast and mesenchymal cells, whereas Bcl-2 immunostaining was absent in the cytotrophoblasts, and mild in the syncytiotrophoblasts and mesenchymal cells. Bax immunostaining was moderate in the syncytiotrophoblasts and cytotrophoblasts, however it was mild in the mesenchymal cells. The mean number of syncytial knots was significantly lower in the control group than the hypothyroid group (p< 0.05). Mean thickness of medium size blood vessels was significantly lower in the hypothyroid group than the control group (p< 0.05). Mean area of stromal fibrosis demonstrated in the hypothyroid group was higher than the control group (p< 0.05). Conclusion: We conclude that significant histological changes occur in the placentas of hypothyroid mothers with associated high incidence of apoptotic marker response. © 2010 by Türkiye Klinikleri.