Participants discriminated between tripelennamine and placebo in experiments differing in instructional set. In 1 experiment (SED), participants were told that 1 of the 2 drugs was more sedative-like, and during the other (STIM), 1 was more stimulant-like. During generalization tests, participants received diazepam or d-amphetamine. Percent correct was the same in both experiments. Tripelennamine increased sedative and decreased stimulant effects. Amphetamine and diazepam produced typical subjective effects. Some subjective effects differed across experiments with more sedative and less stimulant effects during SED than STIM. In SED and STIM, capsules were labeled 80% of the time as a sedative and stimulant, respectively. Thus, instructions designed to give expectations had no effect on discrimination and only a few changes in subjective effects. When asked to name the drug that they believed they received, labels reflected instructional set.