This study was designed to determine whether serum C-reactive protein (CRP) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy. A one-day or ten-day regimen of cefadroxil (30 mg/kg/day in two divided doses) was assigned randomly to 80 children who had acute urinary tract infection and CRP concentrations less than 28 microgram/ml (CRP-negative group). Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values greater than or equal to 28 microgram/ml (CRP-positive group). The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to, but different from those of children with CRP-positive infections. Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day (44.4%) compared to ten days (20%) of cefadroxil therapy (P less than .05). When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children, a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics (79%) compared to recurrences after the standard ten-day regimen (41%). Additionally, the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy (48%) as opposed to conventional therapy (34%). These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in children with CRP-negative urinary tract infection.