R ecently introduced statistical tools capable of discerning differences between the pattern of luteinizing hormone (LH) secretion and that of follicle-stimulating hormone (FSH) could be valuable in understanding ovulation and menopause, and ultimately in making diagnostic decisions and treating infertility and polycystic ovary syndrome. We assessed the validity and scope of the hypothesis that FSH is secreted more irregularly than LH in ewes and fertile women. We compared secretory irregularity of LH to that of FSH in both ovariectomized ewes (n = 7) and women of proven fertility (n = 5) during the follicular and luteal phases of their reproductive cycles. In each sheep, time series from both hypophyseal portal blood (HPB) and peripheral blood were evaluated in 72 samples obtained every 5 min; in each human, both luteal and follicular periods were studied in 192 samples obtained every 7.5 min. To quantify serial irregularity, we used approximate entropy (ApEn), a scale- and model-independent statistic. FSH secretion was consistently more irregular than that of LH in each subject. For sheep HPB, ApEn(FSH) = 1.415+/-0.097 was larger than ApEn(LH) = 0. 822+/-0.213, P < 0.0001 (mean+/-SD, paired t test). This difference persisted peripherally: ApEn(FSHper) = 1.431+/-0.101 > ApEn(LHper) = 1.252+/-0.086, P = 0.024. In women, ApEn(FSH) = 1.467+/-0.217 > ApEn(LH) = 0.923+/- 0.305, P < 0.0001. ApEn(FSH) > ApEn(LH) in 100% of women (peripheral) and sheep HPB. Secretion during the follicular phase was more irregular than during the luteal phase for both FSH and LH (P < 0.01). LH mean level secretion showed a wake/sleep difference in women, P < 0.005, with higher values awake. The consistency and statistical significance of these findings suggest that this LH/FSH difference may be broadly based within higher mammals. Ranges of normative and abnormal regularity values of LH, FSH, and their difference can be used in a number of settings, both (currently) research and (potentially ultimately) clinical milieus.