This study assessed the acute effects of Δ9-tetrahydrocannabinol (THC) on learning and performance, using a repeated acquisition and performance paradigm, in eight healthy adult humans. Subjective ratings of drug effects were also collected. In each component of a multiple schedule, subjects completed a different sequence of 10 responses using three keys of a numeric keypad. In the acquisition component, subjects learned a new sequence with each series of 20 trials. In the performance component, the sequence remained constant throughout the study. The multiple schedule and rating scales were presented pre-drug, post-drug and at 30 min intervals thereafter for 5h. THC (10–20 mg, p.o.) increased the peak percentage of errors during the acquisition component from 7.0% to 9.3% but responding during the performance component was unchanged. THC decreased Digit Symbol Substitution Test performance, increased Profile of Mood State ratings of confusion, depression and general mood disturbance and Visual Analog Scale ratings of strength of drug effect, good and bad effects, but did not alter Addiction Research Center Inventory ratings. In summary, THC in humans caused a slight learning deficit at behaviorally active doses under the repeated acquisition procedure.