Human papillomavirus (HPV) infection in the genital tract is associated with a number of cytological changes which are accepted as standard criteria for a cytological diagnosis. We evaluated the covariation and diagnostic accuracy of these criteria in 210 patients, i.e. 150 cases who were positive for HPV types 6, 11, 16, 18, 31, 33 or 35, and 60 cases who were HPV-negative by simultaneous Southern blot analysis. This was done by re-examining cervical smears obtained at the same time, without knowing the results of the Southern blot analysis, for the presence of koilocytosis, dyskeratosis-parakeratosis, nuclear smudging, hyperchromasia, binucleation, multinucleation, karyorrhexis and macrocytosis. We found that all these cytological changes correlated with the presence of an HPV infection. However, analysis of variance showed that koilocytosis, dyskeratosis-parakeratosis and karyorrhexis were of particular diagnostic value, while the other features provided little or no additional information. By omitting these features and making the diagnosis when two out of three of the key criteria, i.e. koilocytosis, dyskeratosis-parakeratosis and karyorrhexis were present, we diagnosed HPV infection with a specificity of 100% in 36% of the 150 cases, which were positive by Southern blot analysis. The various HPV types produced different morphological patterns which may reflect differences in action on the host cell. In the individual patient, however, such differences in cytology do not provide a sound basis for distinguishing between viral types.