Abstract Mobile phase and stationary phase parameters that influence stability of silica-based reversed phases are examined under high pH conditions. Mobile phases containing 0.1 M NaOH and variable methanol content were cycled through columns packed with various alkyl-bonded phases. Chromatography of small molecules and %C analysis were used to probe changing chromatographic performance as phase hydrolysis proceeded. It was evident that the rate of bonded phase hydrolysis was increased when the 0.1 M NaOH solution contained a high amount of organic solvent, especially when followed by a high organic-containing acidic wash. C 4 bonded phases were less stable than C 18 bonded phases. In the latter case, low bonded ligand coverage or the lack of endcapping also reduced stability against base hydrolysis. Reversed phases bonded to acid-washed silica showed greater base stability than those bonded to non-treated silica. The use of a silica precolumn did not serve to increase system usefulness. However, the use of soluble sodium silicate in the NaOH solution increased column lifetime for both short ( i.e. C 4) and long ( i.e. C 18) n-alkyl chain reversed phases.