We developed a new experimental model of ascending Candida pyelonephritis in female rats with leukopenia and vesicoureteral reflux. Rats were treated transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days before and transurethrally with diluted acetic acid solution to induce vesicoureteral reflux 1 day before inoculation of Candida albicans strain, ATCC 10259 (containing 10(7) cells). Microscopy revealed acute pyelonephritis in which Candida cells invaded from the fornix and/or papilla into the medulla within 3 days after inoculation. Between 7 and 28 days after inoculation, chronic pyelonephritis reached the cortex. The incidence of pyelonephritis increased gradually and was approximately 80% after 7 days. Candida colony counts of bladder urine specimens obtained by direct puncture were significantly greater in rats with pyelonephritis extending into the parenchyma than in those with pyelonephritis located along the pelvis (p < 0.01). These results suggest that this rat model shows the characteristic feature of ascending pyelonephritis due to C. albicans and that the severity of Candida pyelonephritis can be estimated from Candida counts of bladder urine.