The influence of penicillin G on the in vitro and in vivo ADP-induced platelet aggregation and on the platelet electrophoretic mobility has been studied. The in vitro investigations in presence of penicillin concentrations varying between 1,000 and 10,000 IU/ml of plasma, and doses of adenosine diphosphate (ADP) between 0.3 and 25 μM/ml, have shown that the photometric aggregation, as well as the screen filtration pressure are both decreased, according to the doses of antibiotic and ADP. The electrophoretic mobility is also impaired. The in vivo study of 8 patients submitted to massive penicillin therapy for bacterial endocarditis seems to be in agreement with the in vitro results, and has shown a prolonged bleeding time, an hypoadhesiveness, an impaired photometric aggregation with an early disaggregation and a decrease of the screen filtration pressure and platelet electrophoretic mobility.