Cytomegalovirus infection was studied in 59 seronegative recipients of bone marrow depleted of lymphocytes by counterflow centrifugation. Eighteen patients died within 3 months after bone marrow transplantation without evidence of CMV infection, and they were excluded from analysis. Twenty-eight valuable seronegative patients received marrow from a seronegative donor, and 13 from a seropositive donor. All but 2 patients received acyclovir orally (4 x 400 mg/day) from days -9 to +60. CMV prophylaxis with immunoglobulin preparations was not given. All blood products were prepared from random, CMV-unscreened blood-bank donors. The red cell concentrates were depleted of leukocytes by filtration, and leukocytes were removed from the platelet concentrates by centrifugation. None of the patients with seronegative donors showed any clinical sign compatible with CMV infection. Two nonfatal primary CMV infections occurred in the recipients of bone marrow from CMV-positive donors. One of the 59 patients developed interstitial pneumonia, in this case caused by Pneumocystis carinii. Leukocyte depletion of blood products from random CMV-unselected blood donors appeared to prevent primary infection in CMV-seronegative BMT recipients. We conclude that prophylactic use of immunoglobulin preparations is not necessary to prevent CMV primo-infection in patients receiving leukocyte-depleted blood products and acyclovir prophylaxis during the first 2 months postgrafting.