Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 ± 0.14 to 2.24 ± 0.06 mmol/liter in group A (p < .001), but only from 3.22 ± 0.15 to 2.49 ± 0.10 mmol/liter in group B (p < .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p < .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p < .01) to values slightly below the normal range from days 4 to 6. A similar and significant decrement in TmP/GFR was noted at days 4 and 6 (p < .01) which was related to the rise (p < .01) in plasma parathyroid hormone concentration from days 4 to 9. Urinary hydroxyproline excretion decreased significantly (p < .01) in both groups from days 0 to 9, with a trend to reincrease from day 6 on in group B. We conclude that a single intravenous dose of AHPrBP is effective in the treatment of tumor-induced hypercalcemia; but 60 mg has a more pronounced and prolonged effect than 30 mg, achieving normocalcemia in al patients, while 30 mg normalized plasma calcium only in moderately hypercalcemic patients. The decrease in plasma calcium after a single day infusion of 60 mg is similar to that previously observed during treatment of 30 mg per day during 6 days.