Placental protein 14 (PP14), originally isolated from the human placenta and its adjacent membranes, was detected in the serum of nonpregnant women. The levels were measured by radioimmunoassay in 218 serum samples from 19 women throughout the menstrual cycle. In 13 women with a normal ovulatory cycle, the levels showed consistent variation. They were highest (up to 172 ng/ml) in the late secretory phase and remained high for the first days of the next cycle. Low concentrations were found from the midproliferative to the early luteal phase of the cycle. No similar variation was seen in anovulatory cycles of six other women. Compared with ovulatory cycles, anovulatory cycles exhibited lower PP14 levels in the latter part of the cycle (P less than 0.001) and in the beginning of the next cycle (P less than 0.01). In ovulatory cycles, the sustained elevation of serum PP14 concentration over the following period may be explained by the fairly long half-life (42 hours) of PP14 in serum: once the level has increased, it declines slowly. These results suggest that PP14 measurement may become a novel means to distinguish between ovulatory and anovulatory cycles even after the onset of the next period.