Background Major depression is associated with activation of the inflammatory response.Aims To examine C-reactive protein levels in depression and to determine the impact of selective serotonin reuptake inhibitor (SSRI) therapy.Method A two-part study In study 1, which used a between -subjects design, C-reactive protein was measured in 32 patients (20 currently depressed, 12 euthymic) with a history of DSM - IV major depression, all of whom were treated with an SSRI, and in a healthy comparison group (n=20). Study 2 employed a within-subject design: C-reactive protein was measured in 20 patients with major depression both before and after SSRI treatment.Results In study 1, C- reactive protein levels did not differ between the group with depressive disorder (either currently depressed or euthymic) treated with SSRIs and the healthy group. In study 2 the protein levels dropped significantly following treatment with antidepressant medication.Conclusions Following SSRI treatment for major depression there is a significant drop in C-reactive protein concentrations whether or not the depression resolves. These findings indicate that antidepressants induce an anti -inflammatory response independent of antidepressant action.Declaration of interest T.G.D. has lectured at meetings sponsored by or acted as an advisor to all companies who market a branded SSRI.