Thirteen patients with hypercalciuric calcium nephrolithiasis continued to form calcium stones when treated with thiazide (4.69 +/- 6.62 [mean +/- SD] stones per patient-year to 5.12 +/- 10.87 stones per patient-year), despite adequate hypocalciuric response (a reduction in urinary calcium levels from 303 +/- 119 mg per day to 193 +/- 88 mg per day, p less than 0.01). Because they had hypocitraturia (250 +/- 86 mg per day versus 643 +/- 236 mg per day in normal subjects, p less than 0.001), potassium citrate (10 to 20 meq three times per day) was added to the ongoing treatment program. During combined treatment with thiazide and potassium citrate, urinary pH significantly rose, and normal levels of urinary citrate were restored. Ten patients stopped forming new stones and all 13 had reduced stone formation rate. Thus, potassium citrate supplementation should be considered in patients requiring thiazide therapy for the control of hypercalciuric nephrolithiasis, especially if they have concurrent hypocitraturia or if it develops during thiazide therapy.