Long-term effects of potassium citrate therapy (usually 60 mEq/day) were examined in 53 patients with renal stones (11 with uric acid lithiasis with complication of calcium stones, 10 with hypocitraturia as the sole abnormality, and 28 with hypocitraturia occurring with other abnormalities such as absorptive hypercalciuria, renal tubular acidosis, hyperuricosuric calcium oxalate nephrolithiasis, and enteric hyperoxaluria). Potassium citrate was given alone in 29 patients, added to thiazide and/or allopurinol treatments in 12 patients who continued to form stones on these treatments, and begun concurrently with thiazide and/or allopurinol in 12 patients with hypocitraturia and other defects (hypercalcuria and/or hyperuricosuria). In all three groups of patients, urinary citrate and pH significantly increased during potassium citrate treatment. Urinary saturation of calcium oxalate significantly declined while that of brushite remained unchanged. The propensity for the spontaneous nucleation of calcium oxalate, determined from the minimum amount of added oxalate required to elicit precipitation, declined. The treatment was effective in preventing new stone formation in all three groups. Stone passage rate declined from 5.14-7.41 stones/patient year before potassium citrate treatment to 0.66-1.33 stones/patient year during treatment, and 75.0-91.7% of patients were in remission. In patients who relapsed on other treatments (with passage of 5.14 stones/patient year), the addition of potassium citrate to the ongoing treatment program reduced stone formation to 1.33 stones/patient year and caused remission in 91.7% of patients. In 14 of 33 patients with preexisting radiopaque stones, there was radiological evidence of a reduced number of stones after 8 months-2 years of potassium citrate treatment. In conclusion, potassium citrate restores normal urinary citrate, decreases saturation and propensity for spontaneous nucleation of calcium oxalate, and inhibits new stone formation.