The aim of this study was to evaluate the effect of increasing postnatal age on soluble intercellular adhesion molecule-1 (sICAM-1), a very early and sensitive marker of immune activation and response in the serum of newborn infants. Serum sICAM-1 was measured by EIA (T Cell Diagnostics) in 20 healthy adults (controls) and in 43 (24 females/19 males) healthy neonates, of whom 28 were full term, and 15 were born at a gestational age between 35 and 38 weeks of pregnancy, on the 1st, 5th and 30th day of life. Neonatal serum sICAM-1 values showed a very significant increase (P < 0.01) from the 1st day (137.3+/-62.0 ng/ml) to the 5th day (259.3+/-124.0 ng/ml) and then to the 30th day of life (415.0+/-114.0 ng/ml), being significantly lower on the 1st day (P < 0.01), whereas significantly higher on the 30th day of life (P < 0.05), than those in healthy adults (305+/-195 ng/ml). Serum sICAM-1 values on the 1st day of life depended on both the mode of delivery (significantly higher in neonates born vaginally) and the gestational age at birth (significantly lower in those born at a gestational age over 38 weeks). A significant strong correlation was found in sICAM-1 values between the 1st and the 5th day following delivery (rp = 0.77, P < 0.009).The results of this study demonstrate a significant rise of serum sICAM-1 during the 1st month of life in healthy neonates suggesting a progressively increased activation of the neonatal immune system.