A retrospective study of radiologic findings from 50 postmenopausal women who underwent hormone replacement therapy was performed to determine the frequency and distribution of changes in the screen-film mammographic appearance of breast tissue between pretreatment and posttreatment mammography. Twelve (24%) of the women developed increased parenchymal density during a median follow-up of 18 months (range, 6-39 months). Mammographic changes included diffuse increase in density in seven (14%) of the women; increased multifocal, asymmetric densities in two (4%); and cyst formation in three (6%). A greater percentage of women who received estrogen-progesterone replacement (26%, 10 of 38) demonstrated changes than those who received estrogen alone (17%, two of 12), but the difference was not statistically significant. The authors conclude that benign increases in mammographic density associated with postmenopausal hormone replacement therapy are not uncommon, and they suggest that the serial changes observed in some women may diminish the sensitivity of mammography for the earlier detection of breast cancer.