We conducted a seroepidemiological study to evaluate the potential impact of mass varicella vaccination on the transmission of varicella-zoster virus (VZV) in Italy, where vaccination is not mandatory. We tested 3179 serum samples, collected from September 1996 to October 1997, for specific anti-VZV antibodies using a commercially available ELISA. The results confirmed that varicella typically involves children (82.1% seroprevalence among 10- to 14-year-olds) and that the mean age of acquiring the infection seems to be increasing. The results also revealed that southern Italy, compared to the rest of the country, has a greater circulation of VZV and an earlier age of acquisition. The potential impact of mass vaccination among 12- to 18-month-old children on the epidemiological trend of the infection must be carefully considered, in that failure to reach high levels of coverage could lead to an increase in the mean age of acquisition, which is already occurring in Italy.