Sex-differences in pain intensity, threshold, and tolerance have been reported previously. Some chronic pain conditions, such as fibromyalgia, are more prevalent in females than males. While referred pain is a common phenomenon with musculoskeletal pain conditions, few studies have investigated whether it varies by sex. The purpose of this study was to determine if the incidence of referred pain during experimental muscle pain is sex-dependent. Experimental pain was induced via acidic (pH 5.2) intramuscular (IM) infusion of the left anterior tibialis muscle in 69 healthy volunteers (34 M, 35 F). The infusion was maintained at a constant rate (40 ml/hr) for 15 min (10 ml total). Moderate spontaneous pain was induced. Mean (SEM) peak pain ratings (Borg CR10 scale) were not sex-dependent at the primary site: 3.3 ± 0.4 and 2.8 ± 0.2 (p=0.23), for women and men, respectively. Overall, 62% of volunteers experienced referred pain (peak pain °Ý 0.5 on Borg CR10) distally at the ankle. However, referred pain occurred nearly twice as often in women (n=28/35; 80%) than men (n=15/34; 44%) ( Ö2=9.46, p < 0.005). Further, in women the primary site pain was significantly greater than in those with referred pain (3.9 ± 0.4) than those without (1.0 ± 0.2; p < 0.0001) whereas in men there was no difference between groups (2.8 ± 0.4 and 2.7 ± 0.3, p = 0.83). It has been suggested that referred pain, a centrally-mediated phenomenon, occurs when primary pain exceeds a minimum threshold. Our findings support this for the female volunteers, but not for the male. These findings may suggest women are more prone to centrally-mediated referred pain, which may have clinical implications for conditions such as fibromyalgia. We conclude experimental muscle pain results in greater incidence of referred pain in women than men. Funded by grants from IASP and APS. Sex-differences in pain intensity, threshold, and tolerance have been reported previously. Some chronic pain conditions, such as fibromyalgia, are more prevalent in females than males. While referred pain is a common phenomenon with musculoskeletal pain conditions, few studies have investigated whether it varies by sex. The purpose of this study was to determine if the incidence of referred pain during experimental muscle pain is sex-dependent. Experimental pain was induced via acidic (pH 5.2) intramuscular (IM) infusion of the left anterior tibialis muscle in 69 healthy volunteers (34 M, 35 F). The infusion was maintained at a constant rate (40 ml/hr) for 15 min (10 ml total). Moderate spontaneous pain was induced. Mean (SEM) peak pain ratings (Borg CR10 scale) were not sex-dependent at the primary site: 3.3 ± 0.4 and 2.8 ± 0.2 (p=0.23), for women and men, respectively. Overall, 62% of volunteers experienced referred pain (peak pain °Ý 0.5 on Borg CR10) distally at the ankle. However, referred pain occurred nearly twice as often in women (n=28/35; 80%) than men (n=15/34; 44%) ( Ö2=9.46, p < 0.005). Further, in women the primary site pain was significantly greater than in those with referred pain (3.9 ± 0.4) than those without (1.0 ± 0.2; p < 0.0001) whereas in men there was no difference between groups (2.8 ± 0.4 and 2.7 ± 0.3, p = 0.83). It has been suggested that referred pain, a centrally-mediated phenomenon, occurs when primary pain exceeds a minimum threshold. Our findings support this for the female volunteers, but not for the male. These findings may suggest women are more prone to centrally-mediated referred pain, which may have clinical implications for conditions such as fibromyalgia. We conclude experimental muscle pain results in greater incidence of referred pain in women than men. Funded by grants from IASP and APS.