ABSTRACT: Human milk was shown to contain prostaglandin E2 (PGE2) and plasminogen activator (PA) at variable concentrations depending on the time of lactation after delivery. Milk PA was functionally and immunologically identical to urokinase. A follow-up study showed that the maximum PGE2 concentrations occurred during the second week while the maximum PA concentration was observed at the end of the first week of lactation. Milk macrophages cultured in vitro were able to secrete both PGE2 and PA. When cells were activated by concanavalin A (ConA) or E. coli lipopolysaccharide (LPS), PGE2 secretion increased dramatically while PA secretion did not. The ability of activated macrophages to secrete PGE2 was at its highest shortly after delivery. It then progressively decreased during lactation. The possible physiological role of PGE2 and PA on the gastrointestinal tract of breast fed infants is discussed.