The optical isomers of diltiazem hydrochloride Ca-channel blocker were separated by packed-column sub-and/or supercritical fluid chromatography (p-SubFC and/or p-SFC) on a column of modified cellulose coated onto silica, using a mixture of carbon dioxide with a polar modifier and additive. The effect of parameters (Chiralcel columns, modifiers, additive, pressure and temperature) was investigated systematically, and the interactions between the diltiazem optical isomers and chiral stationary phase were discussed, Four optical isomers of diltiazem hydrochloride were achieved with baseline resolution on the Chiralcel OD column within 8 min. To determine three optical impurities in diltiazem hydrochloride, the precision, accuracy, linearity and detection limit were investigated, and the results were sufficiently acceptable. In addition, the resolutions in p-SFC were compared with those in high-performance liquid chromatography. (C) 1997 Elsevier Science B.V.