The goal of this study was to quantify changes in uterine volume during and after chemotherapy for breast cancer. Fifty-eight patients (mean age 42 years) with advanced breast cancer undergoing treatment with FLAC (5-fluorouracil, leucovorin, Adriamycin, and cyclophosphamide) were studied with serial pelvic CT. The transverse, anteroposterior, and sagittal measurements of the uterus were taken in each of the CT scans. The uterine volumes were calculated, normalized to baseline volumes, and graphically displayed for each patient. The temporal changes in uterine volume were correlated to the dates of chemotherapy administration and menstrual status. There was a striking and consistent loss of uterine volume with chemotherapy. This phenomenon was observed in 55 (95%) of the 58 patients. The mean minimum uterine volume was 58.3 +/- 20.2% compared with the baseline. This loss of uterine volume began after the administration of the first cycle of chemotherapy and progressed during subsequent cycles. It coincided with loss of normal menses in all patients. After completion of chemotherapy, there was a recovery of the uterine volume in 12 of the 16 patients who had follow-up CT. The mean recovery uterine volume was 108.4 +/- 49.8% of baseline. Menses recovered in four of these. Chemotherapy causes loss of uterine volume, which usually recovers after the withdrawal of chemotherapy in premenopausal women. This change should not be mistaken for a therapeutic response of primary or secondary malignancy within the uterus or be confused with subsequent uterine changes due to tamoxifen.