Objective: Our purpose was to investigate the effects of various hormone replacement regimens on mammographic breast density. Study Design: Mammographic density was recorded in women participating in a population-based screening program. All women were nonusers of hormone replacement therapy at first mammogram and thereafter reported continuous use of the same treatment: estrogen alone (n = 50) or estrogen in cyclic (n = 75) or continuous (n = 50) combination with progestogen. Mammographic density was quantified according to the Wolfe classification. Results: An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy (52%) than among those receiving cyclic (13%) and estrogen-only (18%) treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. There was little change in mammographic status during long-term follow-up. Conclusion: Regimens of hormone replacement therapy were shown to have different effects on the normal breast. There is an urgent need to clarify the biologic nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk. (Am J Obstet Gynecol 1999;181:348-52.)