A morphometric study of functional and regressing corpora lutea (CL) of guinea pigs (n = 5 per day) was performed on days 9, 12, and 16 of the estrous cycle. On day 9 the functional CL contained ⋍ 750,000 cells, which included 565,200 ± 56,700 (S.D.) endothelial cells or pericytes and 137,300 ± 7,700 luteal cells. Between days 9 and 12 the only significant change suggesting the onset of regression was a reduction in vascular luminal surface area. During this time the number of luteal cells per CL increased to 204,400 ± 34,800 (P < .05), with an accompanying reduction in luteal cell volume from 19.8 ± 1.8 to 14.4 ± 2.4 pl/cell (P < .01). The increase in cell numbers was explicable by cell division, with mitotic indices of 0.83% and 0.97% on days 9 and 12, respectively. Luteal volume was unaltered. Between days 12 and 16, the mean volume of a single CL fell from 3.98 ± 0.2 to 1.42 ± 0.3 mm3 (P < .01) and luteal cell volume was reduced to 5.3 ± 1.1 pl/cell (P < .01). Between these 2 days the number of endothelial cells per CL fell from 539,900 ± 75,500 to 144,400 ± 63,300 (P < .01), with an accompanying reduction in vascular luminal surface area and in the volume occupied by vascular lumina. The total number of luteal cells per CL was not reduced significantly. It was concluded that luteal cell numbers in the guinea pig increase up to the time of onset of luteal regression, and that during regression up to day 16, shrinkage of luteal cells is the major cause of loss of luteal volume. During regression, endothelial cell loss occurs much more rapidly than loss of luteal cells.