Results from clinical and experimental pain studies provide consistent evidence of sex differences in pain perception, with women reporting more clinical pain and demonstrating lower pain threshold and tolerance levels than men. The present study was designed to assess the notion that sex differences in pain perception may be related to differential activation of supraspinal pain modulation systems. Specifically, the phenomenon of diffuse noxious inhibitory controls (DNIC) was examined in healthy young adult men (n = 39) and women (n = 44) using repeated assessment of nociceptive flexion reflex activity before, during and after exposure to forearm ischemia. Consistent with previous research, women exhibited significantly lower nociceptive flexion reflex thresholds than men, and reported significantly greater pain in response to both forearm ischemia and repeated electrocutaneous stimulation required to elicit the nociceptive flexion reflex. Application of forearm ischemia was associated with a significant decrease in nociceptive flexion reflex activity in both men and women, however, the degree of attenuation of nociceptive flexion reflex activity was not significantly different between the sexes. These findings suggest that men and women exhibit similar activation of diffuse noxious inhibitory controls, but they do not exclude the possibility of sex differences in other forms of central pain modulation.