As plasma 11-deoxycorticosterone (DOC) can arise from adrenal secretion and from 21-hydroxylation of plasma progesterone in extraadrenal tissues, alterations in plasma progesterone concentrations might alter significantly the plasma DOC levels in humans. Therefore, the authors measured DOC in plasma of 6 normal, ovulatory women daily throughout their menstrual cycles and in plasma of normal men. The plasma DOC concentrations in women during the follicular phase, when plasma progesterone levels are low, were also low (42 ± 1.7 pg/ml, mean ± SE). An increase in the plasma levels of DOC and progesterone occurred at midcycle. The plasma DOC levels remained elevated (P <.001, as compared with levels during the follicular phase) throughout most of the luteal phase (119 ± 7.9 pg/ml), declining prior to the onset of menses. However, the plasma levels of cortisol and dehydroepiandrosterone sulfate did not fluctuate during the cycle. The plasma DOC levels in men were 57 ± 4.3 pg/ml (N=10). The authors conclude that, during the ovarian cycle of women, significant changes in the plasma levels of DOC occur that are coupled to fluctuations in plasma progesterone concentrations.