The specific antibody response of 22 renal transplant patients with primary cytomegalo-virus (CMV) infection was compared to that of 21 patients with recurrent infection using seven different techniques to measure antibody. With primary infection seroconversion occurred between two and 12 weeks postoperatively, and geometric mean titers increased rapidly during this interval with each test except virus neutralization. In the group with recurrent CMV infection, geometric mean titers declined slightly initially and then increased rapidly to reach peak levels by 10 weeks. In both primary and recurrent infections, IgM antibody was detectable by radioimmunoassay and indirect immunofluorescence; the former procedure was clearly the more sensitive. After absorption to remove rheumatoid factor, 20 of the 22 patients with primary infection and eight of the 21 with recurrent infection had IgM antibody to CMV by radioimmunoassay which often persisted for over six months. The former group had significantly more viremia and symptomatic infections than the latter. Two critically ill patients failed to develop IgM or neutralizing antibody.