Previous reports have suggested that urease-producing bacteria play a prominent role in the formation of infection-induced urinary stones. We have carried out crystalization experiments in vitro which show that bacterial urease alkalinizes urine, thereby causing: (i) supersaturation with respect to struvite and calcium phosphate; and (ii) formation of struvite and apatite crystals. Growth of Proteus in urea-free urine or in urine which contained a urease inhibitor did not cause alkalinization, supersaturation, or crystallization of struvite and apatite. Growth of Klebsiella, Escherichia coli, or Pseudomonas was not associated with significant alkalinization, supersaturation, or crystallization. Struvite and apatite crystals dissolved in Proteus-infected urine in which undersaturation was maintained by urease inhibition. Similar results in all experiments were obtained using human urine and a synthetic urine which was devoid of matrix, pyrophosphate, or other undefined solutes. Urease-induced supersaturation appears to be the primary cause of infection-induced urinary stones.