Endothelial cells are the most abundant cell type in the corpus luteum (CL), and changes in blood vessels have been proposed to play a pivotal role in CL regression. We have studied quantitatively the changes in the human granulosa-luteal microvasculature in CL of various ages: young (Days 17-19 of the cycle), mature (Days 20-24), old (Days 25-27), early regressing (follicular phase of the following cycle), and late regressing (luteal phase of the following cycle). Blood vessels were identified by immunohistochemical staining for the endothelial cell marker CD34. Because of the anisotropy of blood vessels, both vertical and transverse sections of the granulosa-lutein layer (GLL) were used to estimate relative (volume, surface, and length densities) and absolute (mean cross-sectional area) vascular variables. Full luteinization from young to mature CL was accompanied by a 61% increase in the mean cross-sectional area of vascular profiles and a 52% increase in the mean volume of granulosa-lutein cells, as an estimator of changes in the volume of the GLL. In old and early regressing CL, there was a progressive increase in relative structural vascular variables, due to the shrinkage of the GLL, whereas the mean cross-sectional area of capillaries showed a 53% decrease from mature to old CL. Finally, in late regressing CL, there was a decrease in most relative structural variables, in spite of the increasingly shrunken GLL. The decrease in the capillary diameter found at the late luteal phase most likely leads to a decreased blood flow, and early changes in blood vessels could initiate and/or accelerate CL regression.