Combined in vivo/ex vivo T cell depletion is effective in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but influences the occurrence of active cytomegalovirus (CMV) infection and disease. Twenty nine patients receiving a T cell-depleted marrow graft (Campath-1M) after intravenous application of the monoclonal antibody Campath-1G prior to conditioning were monitored for virus shedding and antigenaemia from day -7 to day +100. In seropositive patients in this group active CMV infection occurred more frequently (10 of 16) and much earlier (nine of 10 until day +21) than in 27 seropositive patients (10 of 27, P < 0.02) receiving cyclosporin A and methotrexate (CsA/MTX). Early active CMV infection after in vivo/ex vivo T cell depletion correlated strictly with an early increase in blood lymphocyte counts (P < 0.01), with predominance of NK cells and/or CD8+ T cells. Three cases of very early interstitial pneumonitis (IP) occurred after in vivo/ex vivo T cell depletion compared with none in the CsA/MTX group. IP was fatal in the only patient with early active CMV infection, who remained lymphocytopenic till death on day +31. This may indicate that an early immune response against CMV is possible and essential for favourable clinical outcome.