In nine studies, 269 healthy subjects or patients underwent exposure to peppermint oil (PO) either by topical intraluminal (stomach or colon) or oral administration by single doses or 2 weeks treatment (n = 19). Methods used to detect effects were oro-cecal transit time by hydrogen expiration, total gastrointestinal transit time by carmine red method, gastric emptying time by radiolabelled test meal or sonography, direct observation of colonic motility or indirect recording through pressure changes or relieve of colonic spasms during barium enema examination. The dose range covered in single dose studies is 0.1-0.24ml of PO/subject. With one exception, which show an unexplained potentiation of neostigmine stimulated colon activity, all other studies result in effects, indicating a substantial spasmolytic effect of PO of the smooth muscles of the gastrointestinal tract. Pharmacokinetic studies reveal that fractionated urinary recovery of menthol is dependent on the kind of formulation used for the application of PO. Optimal pH triggered enteric coated formulations start releasing PO in the small intestine extending release over 10-12 h thus providing PO to the target organ in irritable bowel syndrome, i.e. the colon. The hypothesis is supported by anecdotal observations in patients with achlorhydria or ileostoma, respectively.