The thrombocytopenia that follows infection of C3H/Bi mice with Friend leukemia virus (FV) has been investigated. At various times after infection, megakaryocytes in bone marrow and spleen were collected on Nuclepore filters, stained with the Feulgen procedure, and counted. At the same times, platelets in circulating blood were enumerated by the direct method of Brecher et al., 1963 We found that megakaryocyte numbers decreased within 3 days of infection; platelet numbers began to fall at 7 to 9 days. At 11 days megakaryocyte numbers in femoral marrow and spleen were reduced to less than one-third of control values, platelets to about one-quarter of control values. The data are compatible with the hypothesis that the thrombocytopenia which occurs after FV infection in mice results from the reduction in megakaryocytes that is brought about by the infection. Whether all classes of megakaryocytes are equally affected by FV was next examined. At various times following infection, megakaryocytes in marrow suspensions were concentrated by unit gravity sedimentation and microspectrophotometric measurements of nuclear DNA content were made. The kinetic data showed that, following FV infection, megakaryocytes of high nuclear DNA content were markedly reduced in number, but those of low nuclear DNA content were relatively unaffected. Thus the virus infection may interfere with the normal sequential doubling in DNA content of megakaryocytes and/or it may lead to preferential elimination by the host of those megakaryocytes in the higher DNA classes.