The stereoselectivity of chloroperoxidase halogenation of four substrates has been examined. Chloroperoxidase catalyzes the bromination, but not chlorination, of racemic 2-exo-methylbicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid (to the δ-lactone) and racemic bicyclo-[3.2.0]hept-2-en-6-one (to the 2-exo-bromo-3-endo-hydroxy-bromohydrin). These products are obtained in near quantitative yield and are racemic. The circumstances of the bromination strongly suggest that halogenation does not occur at the active site but rather by chloroperoxidase-catalyzed formation of Br2 and its release into solution. The inability of chloroperoxidase to halogenate these two alkenes at its active site most probably derives from a steric exclusion from the active site. The stereoselectivity of two additional substrates that undergo active site chlorination was determined. Methionine is quantitatively converted to a 50:50 ratio of the two methionine sulfoxide diastereomers. 2-Methyl-4-propyl-cyclopentane-1,3-dione is quantitatively chlorinated to 2-chloro-2-methyl-4-propylcyclopentane-1,3-dione. On the basis of optical rotation and proton nuclear magnetic resonance, this product is present as a 40:60 ratio of the racemic diastereomers. It is concluded that active site chlorination by chloroperoxidase proceeds without appreciable stereoselectivity.