Endovaginal sonography of the endometrium demonstrates characteristic findings throughout the menstrual cycle. To correlate these findings with histologic criteria for normal endometrial development, we compared endometrial biopsies with ultrasonographic findings. Nineteen cycles were monitored in 18 women with ovarian failure whose endometrial cycles were induced exogenously by sequential transdermal 17 beta-estradiol (E2) and intramuscular progesterone. These subjects underwent ultrasonography of the endometrium prior to the day of progesterone initiation (luteal day +1) and continuing throughout the mid-secretory phase. On luteal day +1, ultrasonography characteristically demonstrated a multilayered endometrium consisting of a hyperechoic perimeter (endometrial-myometrial interface), a hypoechoic inner layer, and a hyperechoic midline (luminal interface). By luteal day +7, a gradual increase in echogenicity of the inner layer was detected, while the inner myometrium remained hypoechoic. Eleven of 19 cycles demonstrated a completely hyperechoic endometrium on luteal day +7 and also demonstrated normal stromal development on endometrial biopsies. Three patients who had endometrial biopsies consistent with their chronological development failed to demonstrate a hyperechoic endometrium by luteal day +7. All five biopsies that were histologically out of phase were detected by ultrasonography. Thus, ultrasonography demonstrated a sensitivity of 100% and a specificity of 62% for the detection of histologically normal endometrial development. Endometrial thickness could not be used to discriminate between biopsies that were normal (13 +/- 1.0 mm) and those out of phase (13.8 +/- 1.8 mm). Endometrial histology demonstrated asynchrony of glands and stroma in nine cases in which ultrasonography correlated with stromal, but not with glandular dating, suggesting that the increased echogenicity may reflect stromal edema.(ABSTRACT TRUNCATED AT 250 WORDS)