Modern chemistry topics are often introduced into classrooms long before they appear in standardized exams. This paper investigates the role of a nanoscience context in multiple choice items by using a comparative description of the cognitive load effects of such items on a practice exam that was given to students in 2nd-semester general chemistry and 1-semester pre-engineering general chemistry. It includes a classroom comparison study of performance and mental effort analyses in twelve chemistry content areas including a nanoscience and materials context category. In addition, cognitive load effects of paired items in four subcategories were evaluated. Results from the study shed light on the cognitive load effects of nanoscience and materials exam items when these contexts are included within the undergraduate general chemistry classroom.