New approaches using nonmyeloablative-conditioning regimens have been developed to cause minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However many aspects remain under-evaluated, and few data are available about viral and nonviral infections after these highly immunosuppressive regimens. We present our preliminary data on 21 patients receiving a highly immunosuppressive conditioning strategy, focusing on early infectious complications. Early viral infections before day 45, especially CMV, occurred at a high rate (65%). Furthermore, 33% of patients presented with late bacterial infections (predominately gram negative) although they were not neutropenic compared to conventional conditioning regimens. Although there is presently real interest in these new conditioning regimens which result in reduced immediate transplant-related mortality, it is important that investigators be aware of these pitfalls which may secondarily increase transplant toxicity. Further studies are needed to confirm these findings.