Background: Cannabinoids inhibit gastrointestinal motility. The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase (FAAH). A single nucleotide polymorphism (SNP) in the human FAAH gene (C385A) reduces FAAH expression. Aim: To evaluate associations between FAAH genotype and symptom phenotype, gastric emptying and volume, colonic transit and rectal sensation in patients with functional GI disorders (FGID). Methods: 482 FGID patients [159 constipation disorders, 184 diarrhea disorders (D-IBS), 86 mixed bowel function (M-IBS), 20 chronic abdominal pain, 33 functional dyspepsia] and 252 healthy volunteers (HV) underwent questionnaires and studies of phenotype and genotype from 2000-2007: 250 gastric emptying, 210 fasting and postprandial gastric volume, 152 colonic transit and 123 rectal sensation. All had FAAH genotype [CC vs polymorphic (CA/AA)] determined by TaqMan. Results: FAAH genotype distribution of FGID patients and HV did not deviate from Hardy-Weinberg equilibrium. There was a significant association of FAAH genotype with FGID phenotype (overall X², p=0.011) and with specific individual phenotypes (p=0.048). Thus, FAAH CA/AA increases the odds (relative to HV) for D-IBS (p=0.008), M-IBS (p=0.012) and, possibly, CAP (p=0.055). There was a significant association of FAAH CA/AA genotype with accelerated colonic transit in D-IBS (p=0.037). There was no association of FAAH genotype with rectal sensation thresholds or ratings. Conclusions: The association of genetic variation in metabolism of endocannabinoids with symptom phenotype in D-IBS and M-IBS and with faster colonic transit in D IBS supports the hypothesis that cannabinoid mechanisms may play a role in the control of colonic motility in humans and deserve further study.