To determine the influences of hormone replacement on bone tissue in primary hypothyroidism, a histomorphometric study on undecalcified transiliac bone specimens was performed before treatment in ten patients, during the first month of treatment in 16 patients, and after more than six months of treatment in 15 patients. There were no obvious clinical or biologic signs of excessive replacement therapy. Before treatment, trabecular resorption surfaces were lower and bone cortical thickness was increased. From as early as the first month of treatment, trabecular resorption surfaces and cortical porosity were higher than normal but cortical thickness was still increased. After more than six months of treatment there was a significant loss of trabecular (decreased trabecular bone volume) and cortical (normal mean cortical width; increased porosity) bone with hyperremodeling (increased trabecular resorption surfaces and trabecular osteoid surfaces). This osteoporosis is similar to that observed in hyperthyroidism.