Differences between the pharmaceutical activity among the enantiomers of sotalol are well known, as R-sotalol and S-sotalol have similar antiarrythmic activities but only the R-enantiomer exhibits b-blocking activity. In this study capillary zone electrophoresis was used for the enantiomeric separation of sotalol using different native and derivatized; neutral and charged; cyclodextrines as chiral selectors. The effects of pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The results showed that only the randomly methylated b-cyclodextrine gave a baseline enantiomeric separation under the optimized conditions; chiral interactions being observed also for hydroxypropyl-β-CD and sulfobutyl ether-β-CD. The analytical parameters of the optimized method were verified and the migration order of the two enantiomers was established.