Although there is good evidence of a relationship between certain personality factors (viz. neuroticism and hypochondriasis) in the reporting of somatic symptoms-both in clinical and in nonclinical research-the recognition of the moderating role of individual differences in the frequency and intensity of side effect reporting is virtually absent from drug trial research. This study was a double-blind moclobemide-versus-placebo trial, the purpose of which was twofold: to investigate the degree of side effect complaints in a sample of healthy nonclinical men and women and to assess the role of personality in symptom reporting. Although there was no overall difference between the groups with respect to side effect complaints, there was a highly significant neuroticism x group x time interaction. In both groups, we found the expected positive relationship between neuroticism and symptom reporting at baseline. At the end of the study, however, this relationship was close to zero in the moclobemide group and had increased to close to 0.60 in the placebo group. These results were essentially replicated when neuroticism was substituted in the regression model by a psychometric measure of hypochondriasis. Our findings provide a striking demonstration of the role of personality factors in the placebo adverse response. As well, they indicate that adverse reactions to the medication were also linked to personality differences. Taken together, our results underscore the importance of considering individual differences in all aspects of pharmacologic research that involve subjective interpretation on the part of patients and subjects.