Racemic 7-phenyl-9,10-dioxo-1-aza-8-oxabicyclo[5.2.1]decane (1), a bicyclic 2,4-oxazolidinedione that we previously reported was a possible sodium channel anticonvulsant, was resolved into its enantiomeric forms, the absolute configurations were determined, and the stereoisomers were evaluated for relative sodium channel binding and whole animal anticonvulsant activities. Similar studies were carried out with two monocyclic models, 5-ethyl-5-phenyl-2,4-oxazolidinedione (2) and 5-ethyl-3-methyl-5-phenyl-2,4-oxazolidinedione (3). None of these isomers exhibited stereoselective effects in the sodium channel assay, and only modest enantioselectivities were observed for 2 and 3 in the anticonvulsant assays. (R)-(-)-1 was, however, 4 times more toxic than (S)-(+)-1 in the rotorod test, and due to its larger protective index, (S)-(+)-1 exhibited greater therapeutic potential than either (R)-(-)-1 or racemic 1.