BACKGROUND: Antidepressant prescribing should reflect need. The Quality and Outcomes Framework has provided an opportunity to explore factors affecting antidepressant prescribing in UK general practice. AIMS: To explore the relationship between physical illness, social deprivation, ethnicity, practice characteristics and the volume of antidepressants prescribed in primary care. METHOD: This was an ecological study using data derived from the Quality and Outcomes Framework, the Informatics Collaboratory of the Social Sciences, and Prescribing Analyses and CosT data for 2004-2005. Associations were examined using linear regression modelling. RESULTS: Socio-economic status, ethnic density, asthma, chronic obstructive pulmonary disease and epilepsy explained 44% of the variance in the volume of antidepressants prescribed. CONCLUSIONS: Lower volumes of antidepressants are prescribed in areas with high densities of Black or Asian people. This may suggest disparities in provision of care. Chronic respiratory disease and epilepsy may have a more important association with depression in primary care than previously thought.