To investigate the hypothesis that elevated serum anticholinergic activity is independently associated with delirium in ill elderly persons, the authors performed a cross-sectional study of 67 acutely ill older medical inpatients. The presence of delirium was evaluated with the Confusion Assessment Method, and the presence of many delirium symptoms was measured by the Delirium Symptom Interview. Demographic data and clinical characteristics that may be important for the development of delirium were also collected. Logistic regression techniques demonstrated that elevated serum anticholinergic activity was independently associated with delirium. Among the subjects with delirium, a greater number of delirium symptoms was associated with higher serum anticholinergic activity.