Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post-transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one-yr period of time. By defining leukopenia as a white blood cell count < or =3000 cells/mm(3) and neutropenia as an absolute neutrophil count < or =2000/mm(3), the combined incidence of either leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post-transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti-thymocyte globulin induction, p < 0.05) and/or had rapid steroid withdrawal in the early post-transplant period (44% with vs. 16% without steroid withdrawal, p < 0.05). The most common intervention performed for leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.