Little is known about the relative effectiveness and potency of a variety of treatments for malignancy-associated hypercalcemia, or how beneficial the reversal of hypercalcemia is to these patients. Therefore, 146 trials of treatment for hypercalcemia between 1980 and 1983 at the National Cancer Center Hospital, Tokyo, were evaluated retrospectively. Serum calcium levels exhibited the largest decrease in the mithramycin-treated group (decrease; 5.4 +/- 1.8 mg/dl, mean +/- SD, n = 22), followed by the groups given calcitonin plus glucocorticoids (3.1 +/- 2.3, n = 11), glucocorticoids (2.3 +/- 2.3, n = 18), calcitonin (1.8 +/- 1.6, n = 51), hydration (1.3 +/- 2.5, n = 27), and indomethacin (1.0 +/- 2.3, n = 17). The effective rate was the highest with mithramycin (100%) and then with calcitonin plus glucocorticoids (73%) and with glucocorticoids (61%); it was less than 50% in the other modalities of treatment. In patients with pretreatment serum calcium levels of 14 mg/dl or more, the survival rate improved significantly in those whose serum calcium levels decreased below 12 mg/dl compared with those whose serum calcium remained above 12 mg/dl (50% survival; 35 vs. 9 days, P less than 0.01). These data provide a good guideline and a rationale in choosing the modality of treatment. In addition, the data show that the gain in the survival time achieved by successful treatment of hypercalcemia is clinically significant, because it is long enough to conduct additional antitumor therapy.