Abstract The effects of cyclodextrins on the chemical stability of several mitomycin antibiotics in an alkaline medium have been investigated. A stability-indicating high-performance liquid chromatographic method was used to determine the overall degradation rate constants. The influence of various parameters such as structural variations of the cyclodextrins and mitomycins, temperature and pH was studied. It appears that complexation is most favourable with γ-cyclodextrin. All mitomycin—γ-cyclodextrin complexes degrade at lower rates than those of the free drugs. Moreover, it was shown that γ-cyclodextrin influences the equilibrium between mitomycin C and its zwitterion mesomer.