Experimental and clinical studies have been performed to determine whether Ureaplasma urealyticum has an etiological role in the development of infection stones in the urinary tract. Incubation of synthetic urine in vitro with U. urealyticum caused alkalinization of the urine and crystallization of struvite and calcium phosphate. Inoculation of U. urealyticum into rat bladders resulted in the formation of struvite stones in 84% of the rats. Furthermore, infection with U. urealyticum markedly increased the adherence of urease-induced crystals to the bladder epithelium compared to normal rat bladders, probably due to elimination of the mucous coat which covers the normal urothelium. Clinically, U. urealyticum has been cultured from voided urine and from the stone in patients operated on for renal stones. U. urealyticum was cultured in voided urine in 31 of 247 patients (13%) with metabolic stones, compared to 43 of 145 patients (30%) with infection stones (p less than 0.001). In the patients where stone cultures were performed, U. urealyticum was found in 2 of 125 patients (2%) with metabolic stones, compared to 10 of 64 patients (16%) with infection stones (p less than 0.001). These observations strongly suggest that U. urealyticum is linked to the formation of infection stones in the urinary tract.