The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a four-week period, and serum concentrations of 17-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared to the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between s-estradiol and s-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. These data hence suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation, and show that adaptation to the cold pressor test may be sex dependent.