The influence of certain local anesthetics (LA) on immune responses was investigated in in vivo and in vitro systems. Since the stabilization of the cell membrane may play some role in the local anesthetic action of LA, the effect of LA on the cell membrane was also studied by measuring the fluidity of the membranes of lymphocytes and liposomes by steady-state fluorescence anisotropy. Male babl/c mice were immunized with sheep red blood cells (SRBC), and LA was injected subcutaneously once a day for 5 consecutive days Thereafter, mice were killed by cervical dislocation, and spleen cells were isolated. LA significantly inhibited rosette forming cells and hemolytic plaque forming cells (HPFC). When sensitized-mouse spleen cells were treated with LA in vitro, significant inhibition of HPFC was observed. In another experiment, non-sensitized spleen cells were isolated from the mouse spleen and immunized with SRBC in the presence or absence of LA in a tissue culture plate for 4 days. Higher concentrations of LA inhibited the production of HPFC, but lower concentrations of LA increased the number of HPFC. LA decreased the fluidity of the plasma membrane of purified mice lymphocytes and the liquid crystalline, state of liposomes made with dipalmitoylphosphatidylcholine. LA suppressed the histamine release from isolated rat mast cells due to compound 48/80 without affecting the content of c-AMP in mast cells. Inhibitory effects of LA on the responses elicited in lymphocytes and mast cells were considered to be bue to the membrane stabilizing effect.