The relationship of the development of uterine adenomyosis with the changes in the cell arrangement and cell membrane permeability, and incidence of DNA fragmentation was examined in mice. In uterine areas showing the invasion of endometrial tissues into musculature, rhodamine-phalloidin staining for actin fibers revealed that the stromal cells ran parallel to the direction of the infiltration, and the muscle cells lost their regular arrangement, unlike those in the normal uteri of control mice. Inner myometrium showed positive fluorescence with Evans blue, which is known to stain only cells with increased membrane permeability. Outer myometrium also became fluorescence-positive, when the disease was advanced to severe state bearing invasion of endometrial tissues into the outer myometrium. No fluorescence with Evans blue was observed in the normal uterine tissues. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL method)-positive nuclei were exclusively found in some smooth muscle cells near both the blood vessels and tip of the invading endometrial tissue. These findings indicate that in adenomyotic uteri, apoptotic cell death developed in certain cells in myometrium, though disrupted cell arrangement and increased cell membrane permeability occurred in almost all of the inner myometrial cells. The increased membrane permeability in the myometrial cells might participate in the local occurrence of cell death near the blood vessels. Therefore, endometrial tissue would invade the myometrium through the space produced by the cell death along the blood vessels.