OBJECTIVE Hypercalcaemia of malignancy (HM) is a common metabolic complication associated with cancer. The hypocalcaemic effects of medications used to reduce serum calcium levels in HM are short lived and relapse in hypercalcaemia is not uncommon. Pamidronate is one of the most commonly used bisphosphonates in the treatment of HM but there are no specific guidelines for the frequency of use of this drug in recurrent hypercalcaemia. This study was conducted to assess the optimum frequency of pamidronate therapy necessary to maintain normocalcaemia in patients with HM. METHODS Thirty-four patients with HM were randomly allocated into two groups and treated with intravenous pamidronate administered every 14th or 21st day for 16 weeks (n = 17 each group). Serum calcium and urinary hydroxyproline creatinine ratio were measured at weekly intervals. RESULTS The calcium-lowering effect of pamidronate was apparent by 48 hours and normocalcaemia was maintained for an average of 15 days. When the drug was administered every 3 weeks, hypercalcaemia and associated symptoms developed in 50% of patients (22 separate episodes) during the 3rd week, before the next dose of pamidronate. The incidence of symptomatic hypercalcaemia was significantly decreased (10%, 8 separate episodes, P < 0.01) and survival was improved (P < 0.05) in patients who received pamidronate every 2nd week, thereby minimizing the unpleasant and potentially dangerous effects of hypercalcaemia. CONCLUSIONS Intravenous pamidronate 60 mg/dose, administered every two weeks, can maintain normocalcaemia in the vast majority of patients with hypercalcaemia of malignancy.