Thirteen derivatives of 3-phenyl-2-piperidinone were synthesized and evaluated for anticonvulsant activity. The most active compounds from this group included two simple lactams, 3-hydroxy-l-methyl-3-phenyl-2-piperidinone and 3-methoxy-3-phenyl-2-piperidinone, and two IV-ethoxycarbonyl lactams, l-(ethoxycarbonyl)-3-hydroxy-3-phenyl-2-piperidinone and l-(ethoxycarbonyl)-3-methoxy-3-phenyl-2-piperidinone, whose anticonvulsant activity was comparableto or better than that for valproic acid. Four related acyclic amides were also prepared, but these were essentially inactive as anticonvulsants. © 1984, American Chemical Society. All rights reserved.