We describe how the histology course we teach to first-year medical students changed successfully from using glass slides and microscopes to using virtual slides and virtual microscopes. In 1988, we taught a classic medical histology course. Subsequently, students were loaned static labeled images on projection slides to introduce them to their microscope glass slides, and we made laser disks of histological images available in the teaching lab. In 2000, we placed the static labeled images and laboratory manual on the Web. We abandoned the Web-based approach in 2001. Faculty selected specific areas on microscope glass slides in student collections for scanning at a total magnification of 40, 100, 200, or 400. Christopher M. Prince of Petro Image, LLC, scanned the glass slides; digitized, encoded, and compressed (95%) the images; and placed them on CD-ROMs. The scanned images were viewed up to a magnification of 400 using the MrSID viewer (LizardTech software) and the computer as a virtual microscope. This viewer has many useful features, including effective microscope and telescope functions that provide greater versatility for sample study and speed in localizing structures than was possible with the actual microscope. Image detail is indistinguishable from that viewed under the light microscope at equivalent magnifications. Static labeled images were also placed on CD-ROMs to introduce students to the virtual slides. Students could view all the images on their CD-ROMs at any time and in any place with their laptop computers without going online. Students no longer rented light microscopes in 2002. Both students and faculty have shown strong support for using this approach to teaching histology during the past 2 years. Anat Rec (Part B: New Anat) 275B:196–206, 2003. © 2003 Wiley-Liss, Inc.