Three different tests for detection of antibodies to human cytomegalovirus (CMV), complement fixing with antigen prepared by freeze-thaw disruption (CF-FT) or with antigen prepared by extraction with alkaline glycine buffer (CF-GE) and immunofluorescent staining (FA), were compared in renal transplant recipients and their healthy donors, FA and CF-GE tests yielded positive results at an identical and significantly higher frequency than CF-FT in both donors and recipients. CF-GE and FA performed on donors and recipients predicted all virus shedding post-transplant, whereas CF-FT did not. In the individuals who developed primary infection concurrent with the transplanted kidney, FA developed earlier than other antibodies in about one-half and at the same time in the remainder. In addition, the FA test could be completed more quickly and all sera could be interpreted, which made the FA test more useful than the CF-GE, but both of these tests were clearly superior to CF-FT.