Some basic concepts and trends which appear to be essential in the search for biological markers in mental disorders are discussed. Comments related to major psychosis and alcoholism are presented under three headings: (i) heterogeneity of disorders (ii) multifactoriality of disorders and (iii) mental disorders as genetically influenced disorders. Tentative classification and terminology of biological markers are given. Various types of phenotypic markers are discussed and alcoholism is taken as a model for a more detailed discussion of available putative phenotypic markers and of research strategies to be used, namely the pharmacological challenge in high risk subjects (e.g. ethanol and TRH challenge). Some highlights from the field of DNA markers are described, mainly the basic procedures which may be used to investigate genetic aspects of mental disorders by recombinant DNA technology.