We studied the effects of intravenous alendronate on disease activity in 36 patients with active Paget's disease of bone. Alendronate was administered to 3 groups of 12 patients at doses of 2.5, 5, and 10 mg intravenously daily for 5 consecutive days. The patients were matched for disease activity. Symptomatic improvement was seen in at least 10 patients in each treatment group. Alendronate induced a dose-dependent suppression of biochemical indices of bone turnover in all patients. A significant reduction in the mean fasting urinary excretion of hydroxyproline occurred within 2 days of starting treatment, reaching a nadir at 2-4 weeks, which was most marked in patients receiving 10 mg of alendronate (p < 0.05). There was a slower fall in serum alkaline phosphatase activity with maximal suppression occurring 3 months after the start of treatment. The degree of suppression was least for those receiving 2.5 mg of alendronate (p < 0.05) but no difference in response was observed for the other dosages. The duration of response was also dose-related. A significant fall in the serum calcium and urinary excretion of calcium occurred from the second day of treatment but returned to pretreatment values by 4 months. A transient fall in the mean lymphocyte count was observed, which was similar for each group. This was associated with a short-lived fever in 3 patients receiving 10 mg, in 4 patients receiving 5 mg, and in 2 patients receiving 2.5 mg.(ABSTRACT TRUNCATED AT 250 WORDS)