Antiserum to ICP 10, a herpes simplex virus type 2 (HSV-2) protein that is expressed in cells neoplastically transformed by viral DNA sequences within the Bgl II/Hpa I CD fragment, specifically precipitates the ICP 10 protein from HSV-2 infected cells and stains cells infected with HSV-2 for 4 to 16 hrs by indirect immunofluorescence. At 4 hr post infection (p.i.), the staining is primarily perinuclear, while at 16 hr p.i., it is cytoplasmic and intranuclear. Compartmentalization studies indicate that the35S-[L]-methionine labeled ICP 10 is detectable in both the cytoplasmic and nuclear fractions early and late in infection. However, in its phosphorylated form, ICP 10 is undectable in the nuclear fraction late in the viral reproductive cycle. Anti-ICP 10 serum stains a high (75%-83%) proportion of cervical tissue with pathological findings of dysplasia or carcinoma, as well as atypical exfoliated cells from these patients. Cervical tumor tissue from 4 of 12 patients also stains with antiserum to another purified viral protein complex designated ICP 12/14. In the majority of atypical cells with mild or moderate changes, ICP 10 localizes in the cytoplasm, while the majority of atypical cells with severe changes also display nuclear staining with anti-ICP 10 serum. While exfoliated atypical cells from 60% of patients with dysplasia are positive for ICP 10, those from only one half of these patients stain also with anti-ICP 12/14 serum and this staining is strictly cytoplasmic. Atypical cells from three patients in these series stain with the anti-HSV-2 serum but are negative for both ICP 10 and ICP 12/14. Exfoliated atypical cells from patients with CIS or invasive cancer stain equally well with all three antisera.