l-phenylalanine (Phe) has been shown to elicit release of the gut hormone cholecystokinin (CCK) and reduce energy intake. Furthermore, studies in some animal models demonstrate potentiation of CCK-induced satiety by estradiol (E(2)). As E(2) is elevated in the follicular phase, we expected greater satiety effects than in the luteal phase when the effects may be antagonized by concomitant elevations in progesterone (P). Women with low dietary restraint were tested over two cycles and received encapsulated Phe or dextrose (control) during both phases within each cycle. Data from 20 women and 32 menstrual cycles were analyzed. Daily energy intake was suppressed by 9% for Phe compared to control and 8% in the follicular versus luteal phase of the menstrual cycle. Significant three-way interactions showed that the effects of condition and phase differed as a function of status on the rigid dietary restraint subscale. Phe suppressed daily energy intake by 15% relative to control in the follicular phase for women in the lower 50th percentile of rigid restraint, whereas for women in the higher 50th percentile group, Phe reduced energy intake by 15% in the luteal phase. The results replicate previous findings showing effects of cycle phase and Phe on food intake. The interaction between variables suggests that rigid restraint status modulates the satiety response to Phe, possibly through effects of reproductive hormones. Further studies are needed to replicate these findings and examine other aspects of satiety that may be altered by rigid restraint status.