Certain authors state that primary genital herpes infections mainly produce cells with ground-glass nuclei, whereas secondary infections produce a higher percentage of multinucleated or single cells with prominent intranuclear inclusions. The cervicovaginal smears of 11 patients with primary genital herpes infection and 16 patients with secondary infection were studied to determine the validity of this differentiation. The percentage per patient of virally infected cells containing distinct inclusions ranged from 0% to 35% in the primary herpes group and 0% to 100% in the secondary herpes group. In eight additional patients, the initial herpes simplex virus (HSV)-positive smear was compared with recurrent positive smears taken from 2 to 120 mo later. No statistical difference in the incidence of distinct inclusions in the infected cells was detected. Finally, primary rabbit kidney and the heteroploid A549 cell cultures were inoculated with herpes viruses and followed by fixation with several agents at various time intervals. Alcohol and Bouin's fixative favored the recognition of distinct inclusions, as did the duration of the infection.