PIP: This research study was designed to determine the relative activator concentration in uterine tissue depressed by, adjacent to, and remote from the IUD and to compare these concentrations to control uterine tissues. Uterine tissue used in the study was obtained following hysterectomy in 22 women wearing IUDs. All analyzed tissues were acquired from uteri containing either Lippes loop D or large Saf-T-Coils. These IUDs had been in place for a minimum of 1 year and a maximum of 8 years. Hysterectomies were performed primarily for indications related to symptomatic pelvic relaxation secondary to multiparity. No patient was taking hormonal medication or contraceptives for 12 months prior to hysterectomy. No cases included specimens with significant uterine pathology other than that related to the IUD. Ovarian cycle phase was determined for all specimens analyzed by histologic criteria on adjacent slices of the excised samples. Cases included the following phases: menstrual; early proliferative; mid to late proliferative; early to mid secretory; and late secretory. The myometrium contained considerably more extractable activator than the endometrium in terms of activity per milligram of tissue protein. Variation of endometrial plasminogen activator (PA) showed the same pattern as did previously analyzed control specimens at different stages of the intermenstrual ovarian cycle. Values reached the highest levels in mid to late proliferative endometrium with a fall during the early to mid secretroy phase to the lowest levels, followed by a rise in late secretory endometrium. Myometrium did not parallel endometrium as closely as reported for control cases. In IUD cases, the highest myometrial levels were encountered in the late follicular phase and a fall occurred in the secretory phase, as was the case with endometrium, but no myometrial rise occurred prior to menses. Comparison of mean activator results of depressed, adjacent, and remote endometrial sites from IUD cases and mean endometrial activator levels from control cases revealed the highest values in IUD depressed endometrial tissues. The next highest were in IUD adjacent endometrium. Significantly lower results occurred in IUD remote endometrial samples. These comparisons were not considered to be biased by interphase differences in activator since equal proportions of all 4 menstrual phases existed among the 3 IUD sampling sites and the total control material studied. In sum, uterine PA activity plays an important role in IUD associated menorrhagia, and the results indicate that it is also important in IUD associated metrorrhagia. The causes of cyclic physiologic fluctuation and of IUD stimulated increases in uterine PA activity are poorly understood at this time.