Some but not all preterm neonates develop inflammatory related conditions in the neonatal period, including sepsis and nocosomial infections. The reasons for this differential response is unclear, but may be related to individual responses to antenatal glucocorticoid therapy in utero. Glucocorticoids exhibit potent anti-inflammatory properties and therefore may suppress neonatal innate immune function leading to the development of these common morbidities. In order to explore this, we characterised the ability for neonatal mononuclear cells, separated from term and preterm cord blood, to respond to a variety of pathogens which activate different toll like receptors. Data was analysed with respect to gestational age and time since antenatal betamethasone exposure. Cytokine production in response to in vitro stimulation by TLR agonists (Peptidoglycan TLR2; Poly I:C TLR3; Lipopolysaccharide TLR4; Imiquimod TLR7; CpG oligonucleotide TLR9) was measured by ELISA. Preliminary results indicate that cord blood mononuclear cells from preterm neonates failed to respond to immunological challenge more frequently than term neonates, (p<0.05). Time between birth and antenatal betamethasone exposure did not explain the differences in response rate. This study suggests that preterm neonates may be more prone to inflammatory conditions in the neonatal period due to a fundamental immaturity in their innate immune response, leaving them unable to recognise and therefore respond to pathogens appropriately. Studies are continuing in our laboratory to identify antecedents and elucidate further the mechanisms leading to an immature innate immune response.