Abstract A number of well known brain—gut peptides are found in the cerebral cortex. Those with the highest concentrations are almost always co-localized with both conventional transmitters (particularly GABA) and/or with other peptides within limited populations of cortical intrinsic neurons. The neurons containing both GABA and a peptide have similar morphology but particular sub-groups can be identified in terms of the peptides they contain and their synaptic targets. Levels of one cortical peptide, somatostatin, decline in Alzheimer's disease without a concomitant decline in GABA, with which it is co-localized. This and certain other puzzling features of peptide action and peptidergic cell morphology suggest that some may mediate trophic, and other effects on cortical neurons.