Orthophosphate was administered in a daily dose of 1.0-1.5 g to 32 patients during a median treatment period of 3.1 years. The patients were followed with repeated serum and urine analyses and KUB radiographs. Urine composition with respect to calcium oxalate supersaturation was favorably affected. There were reductions of urinary calcium (p less than 0.01) and calcium/citrate quotients (p less than 0.001). During the follow-up period 31 new stones were formed by 12 patients. When the rate of stone formation during treatment was compared with that during a period of similar length following diagnosis, there was no difference. On the other hand, 73 stones had formed during a period of similar length before the start of treatment. This demonstrates the problem concerning evaluation of medical prophylaxis. Four of 11 patients treated for a period longer than that expected for new stone formation continued to form stones. Stone formation was also recorded in 8 out of 15 patients with a shorter follow-up. Despite favorable biochemical effects the clinical result with orthophosphate treatment was disappointing, at least with the doses used in this study.