To compare the effects of hydrochlorothiazide (HCTZ) alone and in combination with amiloride on urinary calcium excretion we performed 14 acute studies on 7 patients with vitamin-D-induced calciuria. Each patient was studied first with HCTZ alone, and 1-32 weeks later with the same or lower dose of HCTZ combined with amiloride. Administration of HCTZ alone did not change UCaV during the 1st day of therapy, and caused a significant reduction from 44.4 +/- 28.8 to 26.0 +/- 14.4 mg/m2/24 h (p less than 0.02) on the 4th day. In contrast, combined diuretic regimen caused a significant reduction in UCaV from 36.0 +/- 16.7 to 23.6 +/- 14.4 mg/m2/24 h (p less than 0.02) on the 1st day and further reduction to 13.3 +/- 6.9 mg/m2/24 h (p less than 0.01) on the 4th day. UCaV on the 4th day was significantly lower with the HCTZ-amiloride combination (p less than 0.05). The combined therapy caused a greater reduction in FECa/FENa than HCTZ alone on the 1st day (p less than 0.02) and on the 4th day (p less than 0.01). HCTZ-induced hyperkaluria, hypokalemia and alkalosis were prevented by the addition of amiloride. In another patient, low-dose HCTZ-amiloride had a maximal dissociative effect on FECa/FENa and was more effective than HCTZ given alone in a double dose. 3 patients were treated with the low-dose HCTZ-amiloride regimen for a total of 23 months. UCaV was kept persistently low.(ABSTRACT TRUNCATED AT 250 WORDS)