The G0/G1 to S-phase transition in quiescent EL2 rat fibroblast cells stimulated by mitogen (such as the epidermal growth factor) can be blocked by the addition of morphine to the system. The drug must be actively present when quiescent EL2 cells are induced to enter the proliferative state. Even when morphine is added after mitogenic stimulus, an exposure only within 6 hours is required to inhibit DNA synthesis. These results suggest that morphine can directly influence the proliferation of the nonlymphoid cell system, particularly during the establishment of a competence state (i.e. G0/S phase transition).