The pathophysiology of the postpartum blues, common transient mood disorders in the first week postpartum, has remained elusive. Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS). This study was developed to determine whether the postnatal blues is associated with IRS activation. Serum concentrations of interleukin-6 (IL-6), IL-6 receptor (IL-6R), gp130 (the IL-6 signaling protein), IL-1R antagonist (IL-1RA) and leukemia inhibitory factor receptor (LIFR) were assayed in 22 nonpregnant women and in 91 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the State version of the Spielberger State-Trait-Anxiety-Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum IL-6, IL-1RA and LIFR were significantly higher in pregnant women at the end of term than in nonpregnant women. Serum IL-6, IL-6R and IL-1RA were significantly higher and LIFR significantly lower in the early puerperium than before delivery. The puerperal women whose STAI scores increased in the puerperium had significantly higher serum IL-6 and IL-1RA and lower LIFR. The women whose ZDS scores increased in the early puerperium had significantly higher serum IL-6 and IL-6R concentrations than those without. In conclusion, women with anxiety and depressive symptoms in the puerperium are characterized by IRS activation and by a lowered anti-inflammatory activity in the serum. It is suggested that IRS activation may play a role in the etiopathology of postpartum blues.