Nerve supporting cells were examined immunohistochemically for the expression of S-100 protein and D7 antigen (markers of peripheral Schwann cells) and GFAP (a marker of central-type nerve supporting cells) in pyloric tissue from 18 patients with infantile hypertrophic pyloric stenosis (IHPS) and 10 age-matched controls. In both the IHPS and control groups there was strong staining of the myenteric plexus by all three antibodies. Within the normal pyloric muscle, there was strong staining of nerve fibers by S-100 and D7, but fibers positive for GFAP were considerably less frequent. In the IHPS cases, S-100, D7, and GFAP immunoreactive fibers were either absent or markedly reduced within the hypertrophied circular and longitudinal muscles. Because supporting nerve cells are essential in the maintenance of basic physiological functions of neurons, their absence within the hypertrophied pyloric muscle may be an important factor in the pathogenesis of IHPS.