We have determined blood cyclosporine concentrations using three different methods in a total of 212 therapeutic monitoring specimens from heart, liver, kidney, and bone marrow, transplant recipients. The specimens were analyzed by radioimmunoassay using a polyclonal nonspecific antibody (RIA, Ciclosporin RIA-Kit), radioimmunoassay using a monoclonal specific antibody (SRIA, Sandimmun Kit), and by high-performance liquid chromatography (HPLC). When the nonspecific antibody was used, mean RIA/HPLC ratios in different patient groups ranged from 2.3 to 5.5, and the variability in this ratio was large in all groups. When the specific antibody was used, mean SRIA/HPLC ratios in different groups ranged from 1.1 to 1.5, with smaller variability. It can be concluded that radioimmunoassay using a specific monoclonal antibody is well suited for therapeutic monitoring of blood cyclosporine concentrations. However, even this method overestimates cyclosporine concentrations in certain patients.