In a serological follow-up of 88 women with active invasive cervical carcinoma, antibodies to membrane antigen of Herpes simplex virus (HSV)-infected cells were measured by the use of the mixed hemadsorption method. Sera were collected at the time of initial treatment and then at regular intervals. As controls, 85 healthy age-matched women and 70 patients suffering from other types of cancer were tested similarly. During the 6-to 60-month observation period 16 patients in the cervix carcinoma group died. The reactivity with membrane antigen of HSV-infected cells was positive in 71% of the cervical carcinoma patients, whereas the figure for the other cancer group was 27% and for the age-matched control group 27%. In the group of 16 patients who died, only 3 demonstrated antibodies against surface antigens of HSV-infected cells. In most cases radiation treatment of the tumor did not significantly alter the mixed hemadsorption titer but in 10 surviving patients there was a significant increase in reactivity as the tumor was treated; 1 patient who had recurrence of her cancer lost reactivity in later sera. Among the 11 cervix carcinoma patients in stage I (by clinical definition carcinoma strictly confined to the cervix) all but one showed positive reaction against the surface antigen of HSV-infected cells; the patient lacking reactivity was the only one out of the 11 patients in stage I who had a recurrence of her cancer. The results confirm that low or missing antibody titers to membrane antigen of HSV-infected cells are of prognostic significance, and decreasing antibody titers to membrane antigens run parallel to the severity of the lesions. There was poor correlation between antibody titers against membrane antigens and neutralizing antibody titers.