Transmitter release studies represent a common pharmacological technique, in which a prepared form of neural tissue is stimulated electrically or chemically to induce the release of a given neurotransmitter. This technique has been widely used to ascertain pharmacological properties of drugs and other substances. Due to the lack of availability of human tissue, animal models are widely used as a substitute. Unfortunately, in studies where significant differences in neurochemical transmission between humans and animals are detected, an animal model may prove to be inadequate as a substitute. In this review, limited to studies performed exclusively on neocortical tissue, more than 30 cases of relevant species differences were found. This included quantitative differences such as nerve terminal density of a specific transmitter, or qualitative differences, e.g. different subtypes of receptors in the species investigated. Only original studies were included in this review. There were no restrictions as to the nature of the transmitter, date of publication or measurement of transmitter for the study to be included. The validity of the observed species differences highly depended on the comparability of the experimental conditions, e.g. preparation and origin of the tissue as well as choice of the stimuli for induction of transmitter release.