Between one-fifth and one-third of patients hospitalized on general medicine wards experience significant depressive symptoms during their hospitalization. This study employed 71 general medical in-patients and examined the relative association of illness/hospitalization characteristics, patient characteristics and environmental characteristics with in-patient medical depression. Multiple regression results indicated that in-patient medical depression was related to pre-hospitalization depression and social functioning, patient perception of physician supportiveness and patient perception of illness-related life-disruption. None of the objective illness/hospitalization variables related to depression while in the hospital. These results are interpreted with regard to several current theories in medical psychology including a life-stress model emphasizing the ability of prior disorder to predict subsequent disorder, a social interaction model focusing on the effects of physicians' supportive behaviour on patients' emotional adjustment in the hospital, and models of illness that stress cognitive appraisal in determining illness-related mood and behaviour.