This study examined the specific physiological responses of women with primary dysmenorrhea during the severely painful menstrual (days 1-2 of menstruation) and the non-painful follicular phases (days 5-8 after the onset of menstruation). Subjects consisted of 10 severe primary dysmenorrheic (Group P) and 10 non-dysmenorrheic women (Group C) with regular menstrual cycles. However, only 9 out of 10 and 8 out of 10 subjects of Groups P and C participated during the follicular phase. Physiological measures were taken in a resting state for 60 min. In the menstrual phase, the pain ratings and secretory immunoglobulin A (s-IgA) concentrations of Group P were significantly higher than those of Group C, with relatively significant decreases in the leg-skin temperature in the former as well. In addition, the systolic (SBP) and diastolic blood pressure (DBP) at 45 min after rest in Group P were significantly higher than those found in Group C. These reactions strongly suggest activation of the sympathetic-adrenal-medullary axis (SAM axis) by painful stress. Furthermore, the low-frequency (LF) component of the SBP variability (SBPV) was significantly higher in Group P than Group C, even during the follicular phase. These findings imply that Group P may well have elevated activities of the SAM axis throughout the whole menstrual cycle. As such, it suggests that dysmenorrheic women may be affected by certain stressors other than pain per se and pain-derived emotions throughout the whole menstrual cycle. The findings also indicate that women with dysmenorrhea have more sensitive responses to the SAM system than non-dysmenorrheic women during stress. Moreover, the high-frequency (HF) component of heart rate variability (HRV), or the index for the vagus nerve activity, displayed a consistently higher value in Group P than C. It is postulated that the human body may have responded to pain in an attempt to maintain the homeostatic state by enhancing vagus nerve activity.