Aerobic exercise has been shown to activate endogenous opioid and adrenergic systems and attenuate experimental pain in normal control subjects (NC). In contrast, fibromyalgia (FM) subjects' experimental pain ratings increase after aerobic exercise, suggestive of abnormal pain modulation. In order to determine whether central or peripheral mechanisms are predominantly involved in the abnormal pain modulation of FM patients, the effects of handgrip exercise on thermal (cutaneous) and mechanical (somatic) experimental pain was tested in local as well as remote body areas of FM and NC subjects. Supra-threshold thermal pain ratings and pressure pain thresholds over both forearms were obtained before and during 90 s of sustained 30% maximal voluntary contraction (MVC). This isometric exercise resulted in substantially decreased thermal pain ratings and increased mechanical thresholds in local as well as remote body areas in NC. Opposite effects were detected in FM patients. Thus, sustained local muscular contraction induced widespread pain inhibitory effects in NC. In contrast, the widespread hyperalgesic effects of exercise on FM patients clearly indicate altered central pain mechanisms. However, whether these exercise effects of FM patients result from abnormal descending inhibition or excessive activation of muscle nociceptive afferents needs to be addressed in future studies.