Introduction: Within the last ten years, DAMPs (Damage or Danger Associated Molecular Patterns) have been shown to activate a novel intracellular structure termed the inflammasome (1). Of the four types of inflammasomes that have been discovered, the NLRP3 (cryopyrin) inflammasome is linked to the production of interleukin-1β implicated in the onset of preterm labour. Activation of the NLRP3 inflammasome is complex requiring two ‘hits’ eventually triggering caspase-1 and release of IL-β, reliant, in part, on the purinergic receptor, P2X7 receptor. The hypothesis tested is that the NLRP3 inflammasome is expressed and functional in leukocytes isolated from the villous tissue of the placenta and cord blood. Methods: Placentae and blood samples were obtained with ethical approval and informed consent from pregnant women at term. Leukocytes were purified from placentae, cord and peripheral blood using Ficoll-Hypaque isolation. Immunofluorescence was used to detect the presence of the NLRP protein. IL-1β production was measured by ELISA in the presence of antagonists of the P2X7 receptor and caspase-1, a key molecule of the NLRP3 inflammasome complex. IL-1β production ± drugs was compared using one-way ANOVA for n samples. Results: NLRP3 (cryopyrin) protein was constitutively expressed in peripheral (n=5) and placental (n=8) leukocytes while expression in cord blood leukocytes (n=5) required priming with lipopolysaccharide. IL-1β release was significantly greater (P <0.05) in villous leukocytes (n=8) compared with cord blood leukocytes (n=8) and enhanced further in placental leukocytes of labouring (P<.05; n=6) compared with nonlabouring women (n=7). Production of IL-1 β was significantly inhibited (P<0.05) following preincubation with the caspase-1 inhibitor, YVAD-CHO (n=6) and a selective P2X7 antagonist (n=6) while progesterone (100 nM) treatment reduced this response (P<0.05; n=6). Conclusion: The human placental NLRP3 inflammasome is an important intracellular component mediating the release of IL-1β during pregnancy. Increased production of IL-1β and basal expression of NLRP3 in placental and peripheral leukocytes compared with those of cord blood suggest that the maternally-derived signals have a key role in inflammation during pregnancy.