There is an increasing body evidence pointing to a close integration between the central nervous system (CNS) and immunological functions with lymphocytes playing therein a central role. The authors provide arguments to consider blood lymphocytes as a convenient probe of--an albeit--limited number of cellular functions, including gene expression. The use of brain biopsies of living patients is unrealistic for biochemical investigation, therefore lymphocytes may be a convenient and accessible alternative. Numerous studies showed similarities between receptor expression and mechanisms of transduction processes of cells in the nervous system (e.g. neurons and glia) and lymphocytes. In several neuropsychiatric disorders, alteration of metabolism and cellular functions in the CNS, as well as disturbances in the main neurotransmitter and hormonal systems are concomitant with altered function and metabolism of blood lymphocytes. We summarize relevant investigations on depression, stress, Alzheimer's disease (AD) and schizophrenia. New techniques such as cDNA microarray gene expression and proteomics may give clues to define molecular abnormalities in psychiatric disorders and could eventually reveal information for diagnostic and treatment purposes. Taken together, these considerations suggest that lymphocyte could reflect the metabolism of brain cells, and may be exploited as a neural and possible genetic probe in studies of psychiatric disorders.