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Recently, a few reports have shown that severe depression may be associated with higher levels of positive acute phase proteins (APPs), such as haptoglobin (Hp), alpha 1-acid glycoprotein (alpha 1S) and lower levels of negative APPs (visceral proteins), such as albumin (Alb) and transferrin (Tf). In order to reassess whether depression is related to alterations in the expression of plasma APP concentrations, we measured in 84 normal controls and depressed inpatients positive APPs such as Hp, alpha 1-antitrypsin (alpha 1AT), hemopexin (Hpx), ceruloplasmin (Cp), complement component C3C and one visceral protein, i.e., retinol binding protein (RBP). We found increased plasma concentrations of Hp, alpha 1AT, and Cp in major depressed subjects as compared with healthy controls, with minor depressives exhibiting an intermediate position. RBP was significantly lower in minor and major depressives than in normal controls. The disorders in these proteins were rather sensitive (62%) for major depression, with a specificity equalling 96%. Our findings are compatible with the hypothesis that major depression may be accompanied by inflammatory changes with higher levels of positive APPs (i.e., alpha 1AT, Hp, Cp, alpha 1S) and lower levels of visceral proteins (i.e., RBP, Tf, Alb).