Prolonged (16 h) preexposure to prostaglandin E1 (PGE1) of cells from a murine virus-induced T lymphoma cell line BL/VL3 provoked, in their membranes, a dose-dependent reduction of PGE1-mediated adenylate cyclase stimulation. Smaller (but significant) decreases of helodermin- and isoproterenol-mediated stimulations were also observed. After a 16 h incubation of these cells with 1 microM PGE1, that reduced by 85%, the PGE1-mediated adenylate cyclase stimulation in membranes, 50% of the PGE1 response recovered after 2 h of PGE1 withdrawal from the incubation medium. Over the following 2-24 h time interval, further recovery was limited. Protein synthesis was required for this resensitization mechanism of functional PGE1 receptors coupled to adenylate cyclase, as judged by the inhibitory effects of cycloheximide.