The effect of 2 urease inhibitors, hydroxyurea and thiourea, on experimental ascending pyelonephritis by P. mirabilis was studied in mice undergoing water diuresis. It was found that hydroxyurea significantly diminished the number of bacteria in the kidneys, the severity and number of lesions as well as the number of excreted bacteria. Thiourea, a weaker inhibitor, was less effective. The drugs prevented the establishment of infections but did not eliminate already existing ones. The mechanisms of hydroxyurea action were studied, as this drug also inhibits DNA synthesis. Hydroxyurea did not prevent infections by (urease-negative) E. coli, and selectively suppressed P. mirabilis in a mixed infection with E. coli.