There are many reports which suggest that patients with affective illness (mania and/or depression) have abnormalities in the functioning of one or more neurobiological systems. At a conference convened by the Clinical Research Branch, Division of Extramural Research Programs, National Institute of Mental Health, these findings were reviewed and some of the factors impeding movement towards a more complete and integrated view of the functioning of neurobiological systems in patients with mania or depression were identified. As a result, a multi-research centre, collaborative approach to the study of the psychobiology of affective disorders was developed. In this collaborative programme, which has now been underway for several years, the focus has been upon: (a) the assessment of the functioning of several different types of biological systems in the same patient, both before and during treatment; (b) obtaining a reasonably large number of patients and comparison subjects; and (c) the use within and across centres of standardized diagnostic categories and behavioural rating methodologies. In this paper the history, background, and rationale for this collaborative effort are reviewed. Those biological systems chosen for study are noted, and issues such as reliability and validity of diagnoses, measurement of state variables, assessment of change with treatment, and logistical and coordinating problems are discussed.