The therapeutic effect of cefotiam on experimental urinary tract infections with Proteus mirabilis IFO 3849 in mice was compared with that of cefazolin. The minimal inhibitory concentrations of cefotiam and cefazolin against the test organism were 1.56 and 25 micrograms/ml, respectively. Beginning 3 days after infection, various doses of each cephalosporin were given subcutaneously twice a day for 5 days. Doses of 100 mg of cefotiam per kg or more sterilized the urine within 3 days and effected a marked reduction or complete eradication of bacteria in the bladder walls and kidneys of mice sacrificed the day after treatment was terminated. A dose of cefazolin greater than 800 mg/kg was required for equivalent therapeutic results. Clearance of bacteria from urinary tract organs was as rapid or more rapid with 50-mg/kg doses of cefotiam as with 200-mg/kg doses of cefazolin. Much more rapid clearance was attained with 200-mg/kg doses of cefotiam. The concentrations of cefotiam attained in plasma, kidney, and urine were lower than the cefazolin levels achieved at an equivalent dose. The superiority of cefotiam over cefazolin in treatment of experimental urinary tract infections appears to be due to its greater activity against the test organism.