Expectancy or placebo effects on cognitive function have not been well studied. To determine the effect of taking pills on cognitive function, 40 participants were randomly assigned to a pill or no-pill condition. Healthy seniors who took a 2-week supply of methylcellulose pills, which they were told was an experimental cognitive enhancer, were compared to seniors not taking any pills. There were 2 primary outcome measures defined prior to the study-Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List delayed recall and Stroop color word task time-as well as 7 other cognitive outcome measures. There was a significant effect of pill taking on the 2 primary outcome measures. There was also an effect of pill taking on choice reaction time and Word List immediate recall but not on the other 5 secondary cognitive outcome measures. In an exploratory analysis of potential predictors of the expectancy effect, perceived stress and self-efficacy but not personality traits interacted with the pill-taking effect on cognitive function. Further characterizing and understanding this observed expectancy effect is important to maximize cognitive health and improve clinical trial design.