Changes in the number of osteoclasts in rats after injection of ethylene diamine tetra-acetic acid (EDTA), azetazolamide or colchicine were studied using succinic dehydrogenase staining of osteoclasts. As early as 10 minutes after injection EDTA caused a significant increase in the number of osteoclasts. Azetazolamide and colchicine resulted in a decrease in the number of osteoclasts, apparent after 30 minutes and 60 minutes, respectively. The changes in total serum calcium after EDTA and azetazolamide administration took place at the same rate. However, azetazolamide had an effect which was the reverse of the effect of EDTA. It caused an increase in calcium in spite of a decreased number of osteoclasts. The results of this investigation confirm those of earlier studies, showing very rapid changes in the number of osteoclasts caused by substances giving rapid changes in serum calcium.