Disaggregated chick osteoclasts sedimented onto bovine cortical bone slices excavate deep and sharply defined resorption lacunae that stain intensely with toluidine blue. We have used this observation to develop a simple light microscopic method for quantifying the bone resorptive activity of chick osteoclasts in vitro. Using this technique, we have found that disaggregated chick osteoclasts are strikingly less sensitive than rat osteoclasts to salmon calcitonin (sCT). Bone resorption by rat osteoclasts was completely abolished by synthetic sCT at a concentration of 10 pg/ml. In contrast, sCT at concentrations up to 100 micrograms/ml did not significantly inhibit bone resorption by chick osteoclasts. Bone resorption by chick osteoclasts could, however, be inhibited by prostaglandin E2 at concentrations of 10(-6) M or more. In time-lapse video experiments, the motility of rat osteoclasts was rapidly inhibited by sCT (5-50 pg/ml), prostaglandins I2 and E2 (less than or equal to 10(-4) M), and Bu2cAMP (2.5 X 10(-4) M), whereas chick osteoclasts failed to show such a response. These findings suggest that CT does not play an important role in the regulation of osteoclastic activity in the chick and may explain why injection of the hormone has generally not been found to evoke an acute hypocalcemic response in birds. This fundamental difference in response to CT may limit the utility of chick osteoclast systems as models of mammalian bone resorption.