Human papillomavirus (HPV) is probably a necessary but definitely not a sufficient cause of cervical carcinoma. However, it remains unclear which factors, in addition to HPV, are important for the development of cervical carcinoma and its precursor lesions. To address this issue, we conducted a case-control study nested in a population-based cohort consisting of women participating in cytological screening in one Swedish county, any time during 1969 through 1995. Detailed information on sexual practice, smoking habits and oral contraceptive (OC) use were collected through telephone interviews with 422 case patients diagnosed with cervical carcinoma in situ and 422 control subjects. All cytological smears were analyzed for presence of HPV 16/18 by a polymerase chain reaction (PCR)-based method. Odds ratios (OR) were used as measures of relative risk. After multivariate adjustment, a 2-fold higher risk was observed among current smokers compared with never smokers [OR 1.94; 95% confidence interval (CI 1.32-2.85)], an association apparently confined to women younger than 45 years. Current use of OCs was associated with a 4-fold increased risk overall (OR 3.64; 95% CI 1.91-6.93) with a monotonic increase with increasing duration of use (p for trend < 0.001). The number of sexual partners was significantly, positively associated with risk among HPV 16/18-negative (p for trend < 0.005) but not among HPV 16/18-positive women. Our data confirm the association between smoking and cervical carcinoma in situ, which might be age-dependent. Our results further indicate a relation with OC use and the risk for cervical carcinoma in situ.