Spleen cells from mice infected with Friend leukemia virus were examined by scanning electron microscopy. Whereas splenocytes from normal noninfected animals showed the expected morphologic classes of lymphocytes, including those with smooth surfaces and with numerous villous projections, an alteration of cell type was evident within a few days after infection. Friend leukemia virus caused a rapid decrease in the number of villous cells, with a concomitant increase in the number of cells with smoother surfaces. By the end of the first 1 to 12 weeks after infection the majority of cells were smooth, many showing distinct morphologic changes, including "holes" and a spongy appearance. Nearly all of the splenocytes were abnormal in appearance by days 17 to 30 after infection, with most showing a spongy topography. These changes paralleled the marked immunosuppression induced by Friend leukemia virus infection, as well as the appearance of virus-associated surface antigen on individual splenocytes. Topographic changes evident by examination with scanning electron microscopy were not readily apparent by either standard histology or transmission electron microscopy.