Our aim was to investigate the prognostic implications of a single cervical smear showing cervical intraepithelial neoplasia (CIN) in a group of women with a previous series of negative smears, and to estimate their risk of developing histologically confirmed CIN 3. A retrospective case-control study was set up. It consisted of 171 cases and 513 age-matched controls, all with at least 3 negative and no positive smears between 1981 and 1988 inclusive. In all cases CIN had been diagnosed on cytology in 1989, while the controls had remained negative. The women were followed up to the end of 1995. The outcome was recorded in terms of regression, progression, persistence or surgical treatment. In women with a single smear showing CIN 1 or 2, the risk of developing histologically proven CIN 3 was 14 and 26 times that in women with negative smears. Negative control smears in the short term did not exclude subsequent progression. Thus women with a single cervical smear indicating CIN 1 had a greatly enhanced risk of producing a lesion that demanded intervention. Such cases should be observed closely with repeat smears over a period of at least 6 years.