Random motility and chemotaxis of polymorphonuclear leukocytes (PMN) was evaluated after in vitro exposure to 0, 300, 600, and 900 ng/mL (0.84, 1.68, and 2.52 mumol/L) of indomethacin. PMN were obtained from cord blood of 22 preterm infants of less than 37 wk gestation. For comparison, PMN were obtained from cord blood of seven healthy full-term infants and from venous blood of 10 normal adults. In preterm infants, a significant decrease of random motility and chemotaxis of PMN was noted at all three drug concentrations; impairment of PMN function was dose dependent in the three groups (p < 0.0001), with the greatest effect seen at 900 ng/mL (2.52 mumol/L). Significant impairment of random motility was noted in full-term infants when compared with adults at all indomethacin concentrations and in chemotaxis at 300 and 600 ng/mL (0.84 and 1.68 mumol/L). The study indicates that indomethacin has an adverse effect on PMN random motility and chemotaxis, which is more pronounced in preterm infants.