The ultimate goal of this project is to develop a rational treatment program for urolithiasis in which the treatment is selected on the basis of its appropriate physicochemical effects on stone formation in urine, the correction of the underlying physiologic derangements, and minimal potential complications. This goal will be pursued by four multidisciplinary approaches. (1) Biochemical and physicochemical. Studies will be concerned with the characterization of promoters and inhibitors of crystallization in urine and in stones. (2) Physiological. These studies will consider the model of intestinal absorption of stone-forming substances using triple-lumen technique, role of vitamin D in urolothiasis, and the pathophysiology of hypercalciurias. (3) The mode of action of various therapeutic modalities for urolithiasis. These include allopurinol, diphenylhydantoin and sodium cellulose phosphate. Both physiocochemical and physiological action of modalities will be sought. (4) Diagnosis and therapy of nephrolithiasis. A reliable ambulatory protocol for the diagnosis of various causes of stones will be developed. Working criteria for optimum therapy will be formulated whereby a specific treatment is chosen for a particular cause of stones, on the basis of its ability to "correct" physicochemical and physiologycal derangements. The rational therapy of urolithiasis will have been achieved if during long-term clinical trials, the particular optimum therapy is shown to prevent stone formation, exert appropriate physiochemical effects in urine, correct underlying physiological disorders and cause minimal or tolerable side-effects.