On the basis of almost 15 years of experience with thiazide treatment in 346 patients with calcium stones, we believe that the following conclusions are justified: 1) Stone progression ceases in at least 90% of patients who take hydrochlorothiazide (50 mg, twice daily) on a regular basis. 2) A reduced dose of hydrochlorothiazide, i.e., 25 mg twice daily, appears to be effective in a significant proportion of patients. 3) Thiazides are effective in normocalciuric as well as hypercalciuric patients and in most patients with tubular ectasia (medullary sponge kidney). 4. Side effects necessitate discontinuation of thiazide treatment in approximately 7% of patients. The incidence and severity of side effects is reduced by initiating treatment with a small dose and by increasing the dose progressively until the full maintenance dose is achieved. A trial with a reduced dose is warranted in patients who are unable to tolerate the regular maintenance dose. 5) The therapeutic efficacy of thiazides in stone prevention cannot be accurately predicted by the degree of hypocalciuric response. Stone prevention may cease despite a minimal hypocalciuric response, whereas stone progression may occur when an adequate hypocalciuric response has taken place. 6) In addition to the hypocalciuric action, thiazides reduce urine oxalate excretion and increase urine zinc and (probably) magnesium; these effects probably contribute to the efficacy of this agent in stone prevention.