Some abnormalities of gastrointestinal function are presumed to result from changes in levels of stress-related hormones from the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), represented by adrenocorticotropic hormone (ACTH) and neuropeptide Y (NPY), respectively. We examined the effects of pantethine and fursultiamine on plasma levels of ACTH- and NPY-like immunoreactive substances (IS) in healthy subjects under continual stress from repetitive blood sampling. An open-labelled crossover study was conducted on five healthy volunteers. Each subject was administered a single oral dose each of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240minutes after each administration. Plasma levels of ACTH- and NPY-IS were measured using a highly sensitive enzyme immunoassay. Serial blood sampling increased plasma ACTH-IS and NPY-IS levels, presumably due to stress. Oral administration of pantethine resulted in a significant decrease in plasma ACTH-IS level compared to placebo. Fursultiamine administration resulted in a significant decrease in plasma NPY-IS level compared to placebo. These findings suggest that pantethine and fursultiamine may have modulatory effects on the HPA axis and SNS, respectively, and may be useful to treat postoperative ileus not only by improving gastrointestinal motility but also by ameliorating mental stress.