The effect of medium, molar ratio of buffer to penicillin G sodium, pH, and temperature on the stability of penicillin G sodium was investigated. The stability of penicillin G sodium in various media is in the order of: citrate buffer > acetate buffer > phosphate buffer > sodium bicarbonate > 0.9 % NaCl and 5 % glucose. In the case of the citrate buffer, to maintain stability for a long time, the molar ratio should be higher than 0.75. The degradation kinetics of penicillin in citrate buffer was determined over a pH range of 4.0 to 10.0 and temperatures from (5 to 50) degrees C. By plotting the data of log k versus pH at constant temperature, V-shaped curves were obtained with a minimum around pH 7.0. The plots of ln k versus 1/T at constant pH are linear, and the lines at all pH values are almost parallel to each other. By fitting to the Arrhenius equation, the activated energy obtained is 83.5 kJ.mol(-1).K-1. The best condition to maintain reasonable stability of penicillin G sodium is using the citrate buffer solution with a molar ratio of buffer to penicillin >= 0.75, pH approximate to 7.0, temperature <= 25 degrees C.