OBJECTIVE To evaluate the therapeutic role of gallium nitrate in the treatment of hypercalcemia associated with malignancy and related disease states. METHODS A literature search of English-language studies involving gallium nitrate for the period 1966-1991 using MEDLINE and the bibliographies of relevant articles. METHODS Because of the limited number of studies, all clinical trials were reviewed, with particular emphasis on Phase III comparative trials. Related investigative studies on the pharmacology, pharmacokinetics, and toxicity of gallium nitrate were also reviewed. METHODS Two appraisers independently abstracted data from available clinical trials and evaluated trial quality. RESULTS Two Phase III comparative trials evaluating gallium nitrate in the treatment of hypercalcemia of malignancy have been completed. Gallium nitrate was shown to be superior to both calcitonin and etidronate disodium, based on the comparative percentage of patients achieving normocalcemia and the subsequent duration of normocalcemia. Both trials employed similar methodology. Positive therapeutic effects of gallium nitrate have also been demonstrated in small, noncomparative trials for hypercalcemia associated with parathyroid carcinoma, Paget's disease of bone, and osteolytic bone metastases. CONCLUSIONS Gallium nitrate is effective in the treatment of hypercalcemia associated with malignancy and is appropriate for formulary addition. In certain clinical situations, it may be clearly advantageous over such agents as calcitonin, plicamycin, and etidronate. Further investigation is needed to define the limitations of nephrotoxicity and the therapeutic potential for other indications. Further comparative clinical trials of gallium nitrate versus bisphosphonates and plicamycin could also help define its relative clinical benefit.