The kinetics of degradation of ampicillin (α-aminobenzyl penicillin) in solution was investigated at 35° and constant ionic strength of 0.5 over a pH range of 0.8 to 10. The observed rates, obtained by measuring the remaining intact penicillin, were shown to observe first-order kinetics and were shown to be significantly influenced by general acid and general base catalysis. The catalytic rate constants imposed by citrate and phosphate ions were calculated. In 0.08 N hydrochloric acid solution the apparent rate of reaction was shown to be accelerated with increasing neutral salt concentration and retarded due to the presence of alcohol. In a pH 4.94 buffer no primary salt effect was observed. The apparent heats of activation for ampicillin degradation in solution were determined to be 16.4, 18.3, and 9.2 kcal./mole, respectively, in buffers of pH 1.35, 4.93, and 9.78. The pH-rate profile in buffer solutions showed a minimum at a pH of 4.85. However, at zero buffer concentration the maximum stability was shifted to a pH of 5.85. The agreement between the calculated theoretical curve and the experimental points (buffer-free) supports the hypothesis presented concerning the reactions involved in the degradation of ampicillin in solution.