Prostaglandin E2 (PGE2) is a known negative regulator of T lymphocyte proliferation. Previously we have indirectly evidentiated the involvement of PGE2 in apoptosis of lymphocytes both in vitro and in vivo. We have evaluated a possible direct effect of PGE2 on apoptosis. To this end we have investigated the in vitro effects of PGE2 on cell death, and its possible correlation with c-Myc and Bcl-2 proteins. We used freshly isolated unstimulated human lymphocytes from neonatal thymus, cord blood and adult peripheral blood. PGE2 induced DNA fragmentation in both peripheral and cord blood at 10(-7) to 10(-5) M concentrations, even though this induction was delayed in peripheral blood with respect to cord blood. Apoptosis induced by PGE2 was always associated with a dose-dependent increase of cellular steady state c-Myc protein levels, whereas Bcl-2 protein levels were not substantially affected. Unstimulated thymocytes showed spontaneous DNA fragmentation that occurred earlier and at higher levels in PGE2-(10(-5) M) treated cells with respect to untreated controls. Also in these cells, PGE2 produced an early increase of c-Myc protein expression, although Bcl-2 protein levels remained unchanged. In conclusion, PGE2 induces apoptosis with different kinetics on immature and mature T cells: this induction is associated with the increase of c-Myc protein expression and seems to be independent from Bcl-2 regulation.