Gastrointestinal disorders including abdominal pain, abdominal distention, ileus, and constipation are common after spinal cord injury. In physiologic studies of patients with spinal cord injury, slow gastric emptying, ileal dilation, and abnormal rectosigmoid motility have been found. However, it is not yet known whether abnormal gut hormone release is important in the development of these abnormalities. In healthy volunteers, there are postprandial increases in plasma peptide YY and motilin levels, which appear related to neural mechanisms. We hypothesized that abdominal sympathetic pathways provide tonic inhibition of peptide YY and motilin release and that postprandial increases in these gut hormones are mediated through spinal pathways. Fasting serum was obtained from normal volunteers, paraplegic patients, and tetraplegic patients. In studies in which patients were fed, serum was obtained from normal volunteers, paraplegic patients, and tetraplegic patients before and at 30-min intervals after a 280 kcal meal. Serum motilin and peptide YY levels were measured by radioimmunoassays. In fasting studies, there was a trend (P = 0.23) toward increased fasting serum motilin in paraplegic patients, and this result did not support tonic inhibition of motilin release. Fasting peptide YY levels were not increased in spinal cord injury patients, which did not support tonic inhibition of peptide YY release. In fed studies, there were strong trends toward postprandial increases in serum peptide YY in volunteers and paraplegic patients and a significant postprandial rise in serum peptide YY in tetraplegic patients (P = 0.04). This was evidence against involvement of spinal pathways in postprandial release of peptide YY.(ABSTRACT TRUNCATED AT 250 WORDS)