Background: Patients with affective disorders show evidence of increased positive acute phase proteins (e.g., C-reactive protein [CRP], alpha-1-acid glycoprotein, haptoglobin) and decreased negative acute phase proteins (e.g., albumin, transferrin [TFN]). CRP reductions have been reported to be greater in patients who later respond to lithium augmentation, and these patients also demonstrate higher CRP levels on the failed antidepressant, prior to the addition of lithium. However, association of such systemic immune changes with affective subtypes, mood state, psychotropic medications, age and gender has not been extensively explored. Methods: The present study assessed levels of CRP and TFN in 79 bipolar I, 24 bipolar II, and 46 unipolar depressed outpatients in comparison to 22 healthy controls. Results: Patients on lithium monotherapy were significantly less likely to demonstrate elevated CRP, and a similar trend was noted in those patients taking lithium in combination with an antidepressant. The frequency of elevated CRP levels did not significantly vary for different psychotropic medications, affective subgroups, or mood states. TFN levels were not influenced by diagnosis, affective state or psychotropic medications. Limitations: Due to the retrospective nature of this analysis, the affective subgroups were heterogenous with regard to medications and affective state, and differed significantly in age. Due to limitations in subgroup sample size, significant effects of clinical variables may have been masked by interactions of medications, age, affective subtype, and mood state. Conclusions: The results imply that lithium may play a role in normalizing systemic immune activation associated with depression. Whether such immune changes may be restricted to lithium-responsive subgroups deserves further evaluation. (C) 1998 Elsevier Science B.V.