A stability-indicating, reversed-phase HPLC method was developed to assay betamethasone 17-benzoate in lipophylic bases. An on-line precolumn sample clean-up system was used to protect the analytical column from contamination; it consisted of the Waters Guard-Pak Precolumn Module and the muBondapak C18 Precolumn Insert. The method is simple, specific, accurate, and precise. It is also cost effective because it extends the life of the HPLC column.