Studies on artificial interferences in subjects with no temporomandibular (TMD) history have shown adaptation to the interference within a fairly short period of time. The role of occlusal factors in the etiology of TMD has therefore been questioned. The results might have been different, however, if subjects with a prior TMD history had been included in the study groups. To test this assumption in a randomized double-blind clinical set-up, we included healthy women without (n = 26) as well as with (n = 21) an earlier TMD history. Both groups were randomly divided into true and placebo interference groups. Artificial interferences were introduced in the true interference groups and simulated in the placebo groups. The subjects were followed for 2 weeks, after which the interferences were removed. The subjects without a TMD history showed fairly good adaptation to the interferences, but the subjects with a TMD history and true interferences showed a significant increase in clinical signs compared to the other groups. We suggest that the etiological role of occlusal interferences in TMD may not have been correctly addressed in previous studies with artificial interferences and allow no conclusions as regards TMD etiology.