Psychological stress and work-related burnout in staff working with AIDS and with cancer patients were compared using a self-report method of assessment. Measures included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI), and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were approached responded to the questionnaire, including 70 doctors and nurses working with people with AIDS and 41 doctors and nurses working in oncology. More than a third of staff had substantial levels of psychological morbidity, and about a fifth had significant levels of work-related stress. Factors associated with the presence of high levels of psychological morbidity and with abnormal levels of emotional exhaustion, depersonalization, and concerns about personal accomplishment were identified. Staff described the work situations with which they had difficulty dealing and some of the coping strategies they used. The findings confirm that staff working with people with cancer or AIDS experience psychological difficulties of the kind likely to respond to interventions aimed at improving their ability to cope with work-related stresses. The mental health services could play an important role in carrying out research in this field and in providing practical help to deal with staff's difficulties.