Diabetes mellitus has been associated with a variety of gastrointestinal motor disturbances. Pyloric activity, however, has not been specifically investigated. We have quantified the pyloric manometric profile in 24 diabetics with recurrent nausea or vomiting, or both, without evidence of mechanical obstruction. Twelve healthy volunteers served as controls. A multilumen pneumohydraulic perfusion assembly with five side openings, each 1 cm apart, was positioned fluoroscopically across the antroduodenal junction and used to monitor pressure activity for 5 h (3 h fasting and 2 h fed). Three patterns of pyloric activity were defined and quantified: (a) baseline elevation of ≥ 3 mmHg for ≥ 1 min (tonic pattern); (b) antral-type phasic pressure activity mixed with duodenal phasic activity (phasic pattern); and (c) phasic pattern superimposed on tonic activity (combined tonic-phasic pattern). The duration of the total pyloric activity before and after the meal was greater in diabetics than in controls (p < 0.005). Furthermore, episodes of unusually prolonged (≥ 3 min) and intense (≥ 10 mmHg) tonic contraction, “pylorospasm,” were observed in 14 of 24 diabetics but in only 1 control (p = 0.025). In diabetics, episodes of pylorospasm had a peak amplitude of tonic activity of 13 ± 1 mmHg and a duration of 7 ± 0.7 min (mean ± SE). We conclude that pyloric dysmotility forms part of the widespread disruption of gut motility that affects some patients with diabetes.