This study aimed to examine the effects of one session of hypnosis on the systemic and rectal mucosal inflammatory responses in patients with active ulcerative colitis (UC). In total, 17 patients with active UC underwent a 50-min session of gut-focused hypnotherapy. Before and after each procedure, the systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumour necrosis factor-alpha (TNF-alpha) and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leucocyte count, natural killer (NK) cell number, platelet activation, and platelet–leucocyte aggregate formation. Rectal inflammation was assessed by mucosal release of substance P (SP), histamine, IL-13 and TNF-alpha, reactive oxygen metabolite production, and mucosal blood flow. Eight patients with active UC underwent a control procedure. Hypnosis decreased pulse by a median seven beats per minute; it also reduced the median serum IL-6 concentration by 53%, but had no effect on the other systemic variables assessed. Hypnosis reduced rectal mucosal release of SP by a median 81%, histamine by 35% and IL-13 by 53%, and also, blood flow by 18%. The control protocol had no effect on any of the variables assessed.