• IgG reactive with somatostatin 1-14 was identified in human plasma by enzyme linked immunosorbent assay. From a sample of 25 subjects, six (60%) of ten individuals with major depressive disorder demonstrated antibody reactive with somatostatin 1-14, in contrast to one (7%) of 15 controls. Overall, antisomatostatin reactivity was significantly higher in patients with major depressive disorder (0.233 ±0.177) than in the normal volunteers (0.084±0.039; t= 3.18, P<.01). Antisomatostatin IgG was isolated by affinity chromatography. The recognition site for somatostatin was retained by F(ab)'2 fragments. Although there has been little previous exploration of the existence of antibodies to endogenous neuropeptides, such antibodies could prove of relevance to neuropsychiatric and other human disorders.