The effect of the use of an oral contraceptive (OC) on the frequency of sister chromatid exchanges (SCEs) and on the response in the alkaline comet assay (single-cell gel electrophoresis (SCGE)) was investigated in 18 women taking contraceptive pills daily for 24 months. As controls, fertile women were included with regular menstrual cycles who received no OC drugs. A significant increase in the number of lymphocytes with DNA migration and an increased frequency of SCE per metaphase were observed in OC users as compared with their age-matched untreated controls (P < 0.005). As higher incidences of spontaneous SCEs in peripheral blood lymphocytes have been reported to occur in females during pregnancy due to profound changes in the levels of certain sex hormones such as progesterone and estrogen, particularly during the last trimester, 17 pregnant women served as positive controls in this study in order to test the rate of genetic damage due to those changes. Higher frequencies of SCEs and comet responses were observed in pregnant women than in their matched controls. However, no statistically significant difference in DNA damage was observed between OC users and pregnant women (P > 0.05). This study underscores the fact that prolonged and extensive use of these drugs in our daily life may be hazardous and also, that OC users should be aware of multifactorial risk factors (environmental, genetic and life style patterns) that may be responsible for additional DNA damage. (C) 2002 Elsevier Science B.V. All rights reserved.