Osteoporosis is one of the most serious side effects of glucocorticoid therapy and its development and severity are dependent on the particular glucocorticoid used. A short-term study (15 days) comparing the bone wasting effects and changes in calcium absorption induced by equiactive low and high doses of prednisone, deflazacort (DFZ) and betamethasone, revealed that low and high doses of betamethasone and high doses of prednisone induced a significant decrease in intestinal calcium absorption. No such changes were observed with DFZ. As 1,25-dihydroxycholecalciferol levels were maintained throughout the study, it appears that glucocorticoids impair calcium absorption through a mechanism not involving this hormone. A long-term study (1 year) of equipotent doses showed that all three glucocorticoids caused a decrease in calcium absorption and a progressive decrease in lumbar spine bone mineral content. However, the impairment of calcium absorption and decrease in bone mineral content was least with DFZ. Thus, DFZ appears to offer a degree of protection against both decreased calcium absorption and bone loss.