Rats trained to discriminate between the stimulus properties of 0.6 mg/kg of racemic cathinone and its vehicle, in a two-lever operant task for food reinforcement, were administered doses of S(-)-cathinone, R(+)-cathinone, (+)-cathine and several structurally-related derivatives, in order to study structure-activity relationships. The optical isomers of cathinone and (+)-cathine produced patterns of responding similar to that observed with the training drug; S(-)-cathinone (ED50 = 0.22 mg/kg) was the more active of the two isomers, while R(+)-cathinone (ED50 = 0.72 mg/kg) was more active than (+)-cathine (ED50 = 1.61 mg/kg). In contrast, removal of the alpha-methyl group of cathinone, or substitution at the 4-position of racemic cathinone by a hydroxyl, methoxyl or chloro group, essentially abolished activity at dose levels comparable to the training dose of cathinone.