Many neurotransmitters, related enzymes and receptors are stable post-mortem and can be measured in routine autopsy material. Comparison of brain tissue from control and disease cases can provide evidence of alterations in neurotransmitter systems in mental disorders. However, before attributing a difference in the neurochemical profile to the disease process itself, care has to be taken to exclude non-specific influences such as age, agonal state, drug therapy and post-mortem stability. Changes in a chemical marker can be used to assess the specificity of neuronal loss in degenerative disease but it may be impossible to distinguish such changes from alterations in turnover in surviving neurones. These problems are discussed with particular reference to post-mortem studies of schizophrenia and Alzheimer's disease.