It has recently been proposed that theophylline activates T suppressor systems in vivo and this evidence is further supported by the ability of the drug to attenuate the allograft rejection in humans and in experimental animals. In this study the acute effects of aminophylline on human peripheral blood lymphocyte (PBL) mitogenic responses have been investigated. PBL from healthy young volunteers who received intravenous aminophylline (5 mg/kg i.v. over 20 min) showed an increased proliferative response to phytohaemagglutinin. This was correlated with an augmented OKT4/OKT8 ratio, due to an absolute increase in the OKT4+ subset as well as a decrease in OKT8+ cells. Furthermore, following in vivo aminophylline we observed a significant rise in lymphocyte cAMP levels. These data, together with studies from other laboratories, suggest that the dosages and duration of treatment may influence greatly the theophylline-induced modulation of immune functions.