Based on studies in lymphocyte cultures it has been suggested that endogenous prostaglandins (PG), especially those of the E series (PGE), suppress cell-mediated immune reactions during their induction phase. We have tested this theory in experimental animals using local host–versus–graft (HVG) and graft–versus–host (GVH) reactions in mice. These reactions were suppressed in a dose–dependent manner by treatment of the animals with PGE1. If, however, endogenous PGE was neutralized through treatment of the animals with immune sera directed against PGE (APSE1) then inhibition of the development of HVG and GVH reactions was seen. This inhibition could be abrogated in “add back” experiments by treatment of the animals with PGE1. We suggest that the action of PGE1 during the induction phase of CMI responses is governed by a bell–shaped dose–response curve with a response–enhancing effect at low PGE 1 and a suppressive effect at high PGE1 concentrations. APSE 1 has proved to be very effective in inhibiting responses, and thus treatment with anti–PG antibodies may not only represent a valuable tool for the study of the role of PG in immunoregulation, but may become useful in therapeutic interventions with the immune system—e.g., after bone marrow transplantation.