Since data on human herpesvirus 8 (HHV-8) infection in Spain is not available, our purpose was to determine the prevalence of HHV-8 infection and the risk of developing Kaposi's sarcoma (KS) among organ transplant recipients in different geographical areas of Spain. The study population consisted of 1019 liver and kidney transplant recipients recruited in four transplant units in Spain. Only post-transplant serum samples were available for all participants. IgG anti-HHV-8 latent and lytic antigens were detected by using an indirect immunofluorescence assay as well as enzyme-linked immunosorbant assays. In available samples, HHV-8 DNA genome was detected by using a nested polymerase chain reaction in sera, blood mononuclear cells and KS tissues. The prevalence of HHV-8 infection after transplantation was calculated. To determine risk factors for infection, odds ratios (OR) and 95% confidence intervals (CI) were also calculated. Of the 788 kidney transplants, 5 (0.6%) were HHV-8-positive shortly after transplantation. Of the 231 liver transplant individuals, 8 (3.4%) developed IgG anti-HHV-8 antibodies after transplantation. Thus, incidence of HHV-8 infection is significantly higher among liver transplant recipients in comparison with that in the control population (OR=6, 95% CI=1.2-28.5, p<0.05). In this series, HHV-8 prevalence in liver transplant recipients was higher in the northern (6.6-6.9%) than in the central (2.9%) or the southeastern (1.4%) areas of Spain. Four renal transplant recipients (0.5%) and five of the liver transplant recipients (2.16%) developed KS after transplantation. Time of KS diagnosis after transplant is significantly higher in kidney transplant patients (33.7 months) than in liver transplant recipients (10.4 months), indicating that the latter have a higher risk of developing KS.