To determine if cytologic abnormalities less striking than those usually considered diagnostic could predict the presence of human papillomavirus (HPV). Cervical scrapings were obtained from 403 women and examined by conventional Papanicolaou staining and for the presence of low- and high-risk human HPV DNA. The cytologic smears from 63 HPV DNA-positive and 63 matched HPV DNA-negative patients whose smears were initially read as normal or inflammatory were reviewed by a single cytotechnologist and a cytopathologist, who were blind to the HPV result. The cytologic diagnosis was upgraded to atypical squamous cells of undetermined significance (ASCUS) in nine cases and to low grade squamous intraepithelial lesion in one. All 10 upgraded cases were from the HPV DNA-positive group. A review diagnosis of ASCUS was significantly associated with both HPV in general and the presence of high-risk HPV DNA. Partial koilocytosis and multinucleation were associated with the detection of high-risk HPV DNA, while only partial koilocytosis was associated with the presence of low-risk HPV DNA. Because infection with high-risk HPV types is associated with cervical neoplasia, partial koilocytosis and multinucleation should be viewed with greater concern and possibly added to the ASCUS definition.