Acquisition of the classically conditioned, nictitating membrane response was used to assess effects of LSD on learning. Tone and light conditioned stimuli (CS) were presented 800 msec before delivery of the unconditioned stimulus, consisting of a 100 msec electric shock to the skin over the paraorbital region of the head. Extension of the membrane to the CSs in the 800 msec prior to shock onset was recorded as a conditioned response (CR), while extension to shock onset was recorded as an unconditioned response (UCR). LSD (1, 10, 30, 100 or 300 nmol/kg) was injected i.v., 30 min before each daily conditioning session. Dosages of 1 to 100 nmol/kg of LSD produced a dose-dependent enhancement of CR acquisition. Acquisition to a criterion of 10 successive CRs required 184 trials at 30 nmol/kg of LSD as compared to 293 trials with controls. Separate groups of rabbits received explicity unpaired presentations of stimuli (tone alone, light alone and shock alone). The frequency of responding within 800 msec of CS onset or in the 800 msec before shock onset was low (2-3%) and was not affected by any dosage of LSD, indicating that the effects of LSD on acquisition were not due to sensitization, pseudoconditioning or changes in baseline responding. LSD also had no effect on UCR amplitude. Hence, the systematic effects of LSD on acquisition of CRs reflects the action of the drug on learning.