The association between "nonclassic" cytologic signs of condyloma and human papillomavirus (HPV) infection in women with negative Papanicolaou smears was analyzed via a case-control study. The cytologic signs considered were mild koilocytosis, mild dyskeratosis, binucleation or multinucleation, cleared cytoplasm and nuclear hyperchromatism. The Papanicolaou smears of 166 cases that showed colposcopic and histologic evidence of HPV infection (but whose smears lacked the classic cytologic signs of condyloma) and 166 controls that were negative colposcopically were randomly admixed and blindly reviewed by a panel of cytologists. A significant association to HPV infection was observed for all of the nonclassic signs studied, but multivariate analysis showed a weakly independent association only for mild koilocytosis. The sensitivity (0.46) and the specificity (0.87) of these nonclassic signs were not satisfactory. The utility of selecting women with negative Papanicolaou smears for colposcopy on the basis of these signs is discussed.