Esophageal motility abnormalities, neuropathy, and psychiatric illness were independently determined in 30 patients with type 1 or type 2 diabetes mellitus to clarify the interrelationship of these findings in diabetics. Fifteen patients (50%) were found to have esophageal contraction abnormalities, a specific cluster of manometric derangements. Diagnoses of depression, dysthymia, or generalized anxiety disorder were made in 87% of those with contraction abnormalities but in only 21% of the patients with normal manometric patterns (p = 0.002). Log-linear analysis confirmed that this association was independent of neuropathy effects (p < 0.001). Several changes in individual manometric parameters related to neuropathy alone were appreciated only when the patients with psychiatric illness were excluded from the analysis. These data indicate that some of the esophageal neuromuscular dysfunction observed in diabetics is independent of neuropathy yet is strongly associated with psychiatric disorder. Such findings help to clarify the discrepant relationship of motility disturbances to neuropathy noted in prior reports. We conclude that consideration should be given to psychiatric illness as well as to neuropathy when interpreting manometric features suggestive of autonomic dysfunction in diabetic patients.