d-Lysergic acid diethylamide (LSD), an agonist at the 5-HT 2 A / 2 C and 5-HT 1 A receptors, has previously been demonstrated to enhance associative learning as measured by accelerated acquisition of the rabbit s classically conditioned nictitating membrane (NM) response. The present study examined further the role of these receptors in the action of LSD. LSD (30 nmol/kg, IV) significantly enhanced conditioned response (CR) acquisition to both tone and light conditioned stimuli (CSs), while the 5-HT 1 A receptor agonists 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT; 50 and 200 nmol/kg) and lisuride (0.3-30 nmol/kg) had no effect. Ritanserin (6.7-6700 nmol/kg, SC), a selective 5-HT 2 A / 2 C receptor antagonist, retarded acquisition of CRs to both tone and light CSs in a dose-dependent manner. Ritanserin (6.7-670 nmol/kg, SC) also dose dependently antagonized the enhancement of CR conditioning produced by LSD (30 nmol/kg, IV) to both tone and light CSs. We conclude that the enhancement of CR acquisition by LSD was due to an action at the 5-HT 2 A / 2 C receptor. These results suggest that the 5-HT 2 A / 2 C receptor plays an important role in learning.