Estrogen has been reported to affect aspects of cognition and psychopathology in women, both normal and with psychosis. This study aimed to replicate and extend this research by investigating the effect of estrogen on cognition over the menstrual cycle in a group of normal women and women with psychosis. The sample consisted of 31 premenstrual normal control subjects, and 29 women with psychosis. Subjects were tested twice, 2 weeks apart on a number of cognitive tests. There was no difference in Positive and Negative Symptom Scale scores between the follicular and luteal phases of the menstrual cycle. Both groups of women performed better on the Revised Mental Rotation Test and Trails A during the follicular phase when estrogen levels were low. Contrary to expectation, during the luteal phase, when estrogen was high, the control subjects showed no significant improvement in performance on verbal articulatory-motor tasks, and the women with psychosis performed significantly worse on the Purdue Pegboard. The unexpected adverse effect of high levels of estrogen on motor performance in the psychotic women was hypothesized to be related to their disease process.