Hydrolysis rates were determined for 2'-acetyl erythromycin, three of its homologues (2'-propionyl, 2'-butyryl and 2'-valeryl) and 2'-ethylsuccinyl erythromycin in buffer solution (pH 7.0, 37 degrees C) and in human plasma (37 degrees C) at concentrations of 5 and 100 mg/l. Ester concentrations were measured by fast atom bombardment mass spectrometry. Hydrolysis in buffer followed pseudo first-order kinetics. The half-lives of the esters ranged from 24.3 to 89.5 min (2'-ethyl-succinyl less than 2'-acetyl less than 2'-propionyl less than 2'-valeryl less than 2'-butyryl). Hydrolysis in plasma followed more complex kinetics. The half-lives were generally longer than in buffer and dependent on the initial ester concentration. Apparent first-order half-lives ranged from 35.5 to 492 min (2'-ethylsuccinyl less than 2'-acetyl less than 2'-propionyl less than 2'-butyryl less than 2'-valeryl). In case of homologous esters, the stabilizing effect of plasma and concentration dependence varied with lipophilicity. In buffer solution the hydrolysis half-life of 2'-acetyl erythromycin was dependent on the concentration of alpha 1-acid glycoprotein. Of the homologous esters, 2'-acetyl erythromycin was hydrolysed most rapidly, but it was hydrolysed more slowly than 2'-ethylsuccinyl erythromycin.