Objective. The effects of C-reactive protein (CRP) and tumor necrosis factor- α (TNF- α ) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation. Methods. The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following stimulation with CRP or TNF- α cytokines. Results. PAPP-A mRNA and protein levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and protein levels were achieved after TNF- α stimulation at only 2 and 8 hours, respectively. These findings indicate the dose-dependent effect of CRP and TNF- α stimulation. Actinomycin D treatment completely prevented CRP and TNF- α induction of PAPP-A mRNA and protein expression. Additionally, nuclear factor- (NF-) κ B inhibitor (BAY11-7082) potently inhibited both CRP and TNF- α stimulated PAPP-A mRNA and protein expression. Conclusions. Human PBMCs are capable of expressing PAPP-A in vitro, expression that may be regulated by CRP and TNF- α through the NF- κ B pathway. This mechanism may play a significant role in the observed increase of serum PAPP-A levels in acute coronary syndrome (ACS).