Aims: To investigate the influence of noxious stimulation of the temporomandibular joint (TMJ) on conditioned pain modulation (CPM) and the possible influence of gender on such CPM effects in the craniofacial region of humans. Methods: Twenty healthy men and 20 healthy women participated in two sessions. Conditioning stimulation (CS) was standardized mechanical stimulation of pericranial muscles at a pain level of 5 on a 0 to 10 visual analog scale (VAS). Intra-articular electrical stimuli were applied to the left TMJ with an intensity around VAS = 5 (painful session). No electrical stimulation was applied in the control session. Pressure pain threshold (PPT) and pressure pain tolerance threshold (PPTol) were used as responses to pressure (test) stimuli and were assessed in the right masseter muscle and left forearm before and during TMJ stimulation in addition to the CS (during, immediately after, and 10 minutes after CS). PPT and PPTol were analyzed by multilevel analysis of variance. Results: The parameters were not dependent on gender, assessment site, or session, but were dependent on time (PPT, PPTol: P .001) with session-time interactions (PPT: P .001, PPTol: P = .002). CS triggered increases in PPT and PPTol (hypoalgesia) in both sessions and without significant differences between sessions or assessment sites during CS (painful session: 49.2 ± 3.7%, control session: 46.0 ± 3.4% for PPT and painful session: 17.7 ± 3.2%, control session: 21.4 ± 3.5% for PPTol). Conclusion: Acute noxious stimulation of the TMJ does not alter the magnitude of CPM effects on masseter muscle pain in either gender. It is suggested that deficiencies in CPM in persistent pain conditions are most likely more related to the duration of clinical pain than the pain per se. Schlagwörter: conditioned pain modulation (CPM), experimental craniofacial pain, gender differences, human volunteers, trigeminal system