Immunosuppressive effects of corticosteroids are generally known, but the mechanisms influencing the immune system are poorly understood. However, a correlation between cortisol levels and cytokine production has been reported by several investigators. In the present study we determined cortisol concentrations in human umbilical cord blood. Cord blood samples from healthy and normal term infants born by vaginal delivery and blood samples from healthy adult donors, respectively, were analysed. Our data revealed significantly increased cortisol levels in cord blood. In contrast, samples derived from infants born by caesarian section seem to be normal. Further experiments were performed to analyse the influence of cortisol on the production of interferon (IFN) alpha. Therefore, peripheral blood mononuclear cells (PBMC) were separated from peripheral blood of healthy adult volunteers. Cortisol was added to a final concentration of 30 micrograms/dl as measured in cord blood. Following stimulation with Newcastle disease virus (NDV) the IFN-alpha release was 50 to 60% reduced compared to untreated controls. These data suggest that increased levels of cortisol in cord blood might influence the IFN-alpha response of newborns. We propose that cortisol levels increase transiently after birth and may alter several physiological as well as immunological reactions. Since cord blood is commonly used to investigate features of the neonatal immune system, different behaviour as a result of temporarily increased cortisol concentrations should be considered.