Bone alterations in Paget's disease, have been studied by histomorphometrical evaluation iliac creat bone biopsies before and after long-term treatment with human ans salmon calcitonin. Therapeutic effect was controlled from 12, up to 48 months. All-together 28 bone biopsies were taken from 9 patients (aged 46 to 71 years) with Paget's disease of their os ileum. The biopsies were prepared for histological examination without previous decalcification, cut, stained and quantitatively analysed at the light microscopic level. By means of a point counting method we determined the parameters of bone structure, bone formation and bone resorption. Before therapy was started, trabecular bone alterations could be observed which were typical for Paget's disease of bone as there were bulky trabeculare, increased remodelling surfaces and giant osteoclasts. Following treatment with calcitonin a dramatic reduction of bone remodelling surfaces and a normalization of bone structure occurs. Considering our previous electon microscopy findings, a reduction of the number of osteoclasts as well as their nuclear content, might be explained by an inhibitory effect of calcitonin on cell fusion of osteoclastic precursor cells. In 2 cases, an interruption or hormonal treatment of 5 to 12 months, presented no risk of losing the therapeutic effect.