Fifty donors undergoing plasmapheresis were the subjects of an 18-month longitudinal study of patterns of the activity of complement-fixing (CF) antibody to cytomegalovirus (CMV). Sera, collected monthly whenever possible, were tested with each of three preparations of antigens obtained from the Davis, AD169, and Esp strains of virus. Of 510 sera examined, 321 were reactive with one or more of the antigens; 96% of the reactive sera fixed complement with Esp, 94% with Davis, and 83% with AD169. Patterns of reactivity were determined for 20 of the 39 reactive donors. Multiple fluctuations in titer were observed in 19 of the 20 donors, and 11 individuals vacillated at least once between significant and undetectable (≥1:8 to <1:4) levels. A degree of CMV-strain specificity was observed in some antibody patterns. Donors with labile CF reactivity to CMV did not exhibit concurrent fluctuations in titer on examination with herpes simplex antigen. The antibody patterns suggest that the CMV-host relationship is more dynamic than heretofore appreciated. While not necessarily applicable to the normal adult population, the findings emphasize the necessity for critical interpretation of the clinical significance of titers of CF to CMV.