To explore the time-course and the source of the changes in plasma prorenin that occur in early pregnancy we studied a normal subject (subject 1), an in vitro fertilization (IVF) patient (subject 2) and an ovarian failure patient who received a donor egg (subject 3). Day 0 was the luteinizing hormone (LH) peak (subject 1), the day of human chorionic gonadotropin (hCG) administration (subject 2) or 3 days before embryo transfer (subject 3). In subjects 1 and 2 prorenin increased transiently (three- and ninefold respectively) on days 0-4, then returned towards baseline and began to increase again around day 12 to a maximum (six- and 26-fold baseline) around day 20. Active renin was consistently less than 10% of total renin. In the ovarian-failure patient only small fluctuations occurred in total renin yet her hCG was 137 mlU/ml on day 15, proving that she was pregnant. These results suggest that the prorenin rise that occurs at mid-menstrual cycle and following conception may be due to ovarian prorenin secretion in response to stimulation by gonadotropic hormones.