To prevent renal scarring, which occurs at the end stage of chronic pyelonephritis due to vesicoureteral reflux of infected urine, immediate antimicrobial treatment is reported to be essential. When treatment is delayed, the antimicrobial agent is believed to be effective only in eliminating bacteria, not in preventing scar formation. Using the ascending pyelonephritis model in rats, we investigated the effect of immediate or delayed treatment with ciprofloxacin and that of delayed treatment with a combination of ciprofloxacin and prednisolone in preventing renal scarring following infection. An inoculum of 1 x 10(9) colony forming units (cfu)/0.1 ml. of the HM32 strain of Escherichia coli, which was isolated from a patient with a urinary tract infection, was injected directly into the rat bladder, and the urethra was clamped for 4 hours in each rat. Treatment by ciprofloxacin (15 mg./kg., twice a day for 5 days) alone or in combination with prednisolone (2 mg./kg., once a day for 4 days) was initiated 6 or 72 hours after bacterial inoculation. The kidneys of each rat were examined 6 weeks later. Immediate treatment by ciprofloxacin significantly inhibited renal scarring (no scarring was seen in any of the 8 rats), but delayed treatment had no effect on scarring (4 of 8 rats showed scarring) when compared with the untreated controls (7 of 8 rats showed scarring). However, the addition of prednisolone to the delayed treatment with ciprofloxacin significantly inhibited renal scarring (only 1 of 10 rats showed scarring) when compared with the untreated controls (7 of 8 rats showed scarring). These data suggest that prednisolone is effective in preventing renal scarring which occurs due to vesicoureteral reflux when the initiation of antimicrobial treatment is delayed.