The technology known as virtual microscopy is now widely available to medical students. A number of medical school histology and pathology course directors, including those at the Eastern Virginia Medical School, are exploring the question of how best to make use of this new tool. The current study compared the efficacy of teaching and testing one unit of histology, bone and cartilage, using two technologies, namely, virtual microscopy and traditional microscopy. Additionally, the study examined whether low, moderate, high moderate, or high achieving students perform more effectively in any of the learning/testing formats. In a completely randomized block design, 96 first semester, first-year medical students were grouped by previous exam quartiles then subsequently randomly assigned to one of four groups. Using identical laboratory exercises with highly comparable slides for each experimental group, half of the subjects learned the exercise with traditional microscopy and half learned with virtual microscopy. Subjects were further randomly subdivided into virtual or actual testing groups. The authors found no significant differences in test scores when they examined effects by learning group or by testing group, nor were there significant interaction effects. Student performance evaluated by previous exam quartile was significant (P < 0.001). That is, students who had scored in a particular quartile on a previous test tended to score in the same quartile on the bone and cartilage test regardless of learning or testing method. In a short opinion survey, students were polled to evaluate their experience. Student preferences for both learning and testing method varied widely. Clin. Anat. 20:565–570, 2007. © 2006 Wiley-Liss, Inc.