Controlled clinical trials of acupuncture in FM demonstrate that both sham and real acupuncture are effective at reducing pain. Currently no biological factor has been shown to predict responsiveness to either treatment. Since MORs are implicated in both acupuncture and placebo effects, we investigated the relationship of baseline MOR binding to subsequent pain relief. 18 female FM patients were randomized to receive either one acupuncture or one sham acupuncture treatment. Immediately prior to needle insertion, all subjects underwent a single 40 minute 11C-carfentanil positron emission tomography (PET) scan. Clinical pain was assessed pre- and post-treatment with the Short Form of the McGill Pain Questionnaire (SF-MPQ). PET images were processed with Logan plot analysis resulting in maps of whole-brain MOR binding potential (BP). Since patient expectancies prior to treatment have been associated with placebo effects, we limited our analysis to three brain regions (L caudate, L insula, and L precentral gyrus) that showed significant correlations between MOR BP and expectations of pain relief in all participants. Correlations between changes in SF-MPQ and MOR BP were performed using SPSS v14.0. Both groups displayed clinically meaningful reductions in clinical pain (SF-MPQ total score), but this was not statistically different between groups (mean difference pre-post+SD: acu=4.2+8.9; sham=5.2+5.8; p=0.78). Within the left insula, individual changes in SF-MPQ total score were negatively correlated with MOR BP pre-treatment for the acupuncture group (r=-0.76; p=0.017) whereas in the sham group there was a statistically insignificant trend in the opposite direction (r=0.50; p=0.17). However within the left precentral gyrus, both groups showed similar relationships between MOR BP and changes in affective pain (SF-MPQ affective score; acu: r=-0.68, p=0.04; sham: r=-0.64, p=0.06). Baseline levels of MOR binding within the left insula are associated with differential responsiveness to acupuncture treatment. The mechanism of action of this effect remains to be elucidated.