Lidocaine and Bupivacaine inhibit in vitro 3H-TdR incorporation into peripheral lymphocytes, in a dose dependent ratio, either under PHA stimulus or not. Lidocaine added to cultures at various times from PHA stimulus show a reduced inhibition only when added after the 24th hour. This suggests a sensitizing action of PHA. Lidocaine effect on mitosis of doses between 2000 and 500 micrograms/ml was not completely reversible even when the drug was removed after only 15 min; between 200 and 50 micrograms/ml this effect is reversible. Lymphocyte viability by Trypan Blue exclusion is clearly unrelated to mitotic inhibition; it is however dose related. High Lidocaine and Bupivacaine concentration alter adhesion of cells to plastics and decrease lymphocyte aggregation by PHA. Electrophoretic mobility of lymphocytes incubated with 2000 micrograms/ml of Lidocaine is slower compared to controls; there is no change at 200 micrograms/ml. Local anaesthetics modify steric membrane structure reducing surface charge density. Increased Ca++ in the medium containing local anaesthetic increases lymphocyte stimulation index slightly only for Lidocaine and Bupivacaine doses, which neither alter membrane function nor interfere with lymphocyte viability nor electrophoretic mobility. Increased Na+ and K+ in the medium do not affect local anaesthetic action.