The rate of hydrolysis of the formyl moiety of cefamandole nafate was determined as a function of pH, temperature, and concentration of added sodium carbonate or tromethamine. The reaction rate was sensitive to hydroxide ion in the pH 5.5-8.0 range with half-life values of hours to minutes. Hydrolysis was rapid upon the addition of sodium carbonate or tromethamine. Chirality in the 7-D-mandelamido side chain was unaffected by hydrolysis.