It is wellknown that theophylline yields phenotypic changes on suppressor cells. In the present study we investigated the possibility that theophylline could directly induce a suppressor activity on a lymphocyte subpopulation. We observed that a short preincubation (120 min at 37 degrees C) with theophylline (1mM) activates human peripheral blood lymphocytes to suppress mitogenic response of autologous cells. This activity was not evident on a T cell subpopulation depleted of theophylline-sensitive (T-sens) lymphocytes. Theophylline mediated suppressor activity is only present in the Concanavalin A stimulated cultures, thus suggesting a synergism between Concanavalin A and theophylline in the expression of non specific suppression. Moreover we observed that after a 24 hrs preincubation of lymphocytes in complete culture medium there was a complete loss of theophylline-induced suppression. Such a preincubation time also produced a decrease in the theophylline-mediated enhancement of intracellular 3', 5' cyclic adenosine monophosphate levels and the impairment of E-rosette formation, suggesting that theophylline acts mainly on a "short-lived" suppressor lymphocyte subset.