Intranasal administration of calcitonin (CT) avoids the problem of daily injections in the long-term treatment of osteoporosis. We examined the effect of nasal CT on bone and calcium metabolism in postmenopausal osteoporotic women in a double-blind design. 46 women, 55-75 years in age, and in good general health were included in the study. All patients were at least 6 months postmenopausal and had at least 1 vertebra fracture, bone mineral density (BMD; g/cm2) lower than 0.850 in L2-L4 in a dual energy x-ray absorptiometry (DEXA) AP view of the spine and showed biochemical indications of a fast bone loser. The patients were randomly treated with either nasal CT 200 IU per day, divided in 2 doses (n = 23) or placebo (n = 23) for 1 year. All participants received a daily calcium supplement of 1 g. Clinical and laboratory follow-up every 3 and 6 months, respectively, assessed the clinical picture, bone mineral density measured by DEXA, serum alkaline phosphatase, fasting urinary calcium, creatinine and hydroxyproline. BMD was measured in 4 sites (spine and cervical, Ward's triangle, and the trochanteric area of the hip) before treatment and after 6 and 12 months of treatment. In the placebo group, mean values at the 4 sites showed a 3.3% decrease in BMD after 6 months and a 5.0% decrease after 12 months. In contrast, the calcitonin group showed a 6.8% increase in BMD after 6 months and 11% increase after 12 months (p < or = 0.005). No patient experienced side-effects and there were no complaints of local irritation. We conclude that nasal administration of 200 IU calcitonin daily, continuously for 1 year had a positive effect on the bone mass density in osteoporotic postmenopausal women.