The aim of this study was to investigate the effect of mestranol on pharmacokinetics of paracetamol. The study was carried out on 20 female rabbits. Paracetamol was administered to rabbits intragastrically at a dose of 50 mg/kg b.w. One group of animals was given mestranol intragastrically 0.1 mg once daily during 2 months. The method of Routh A. et al. was used to paracetamol concentration assay. Blood for the assays was collected within 24 hours after drug administration, prior to the study as well as 1 month and 2 months after continuous mestranol administration. The two compartment open model was used for calculations. The study revealed an increase in AUC and paracetamol half-life as well as decrease in the total body clearance. We conclude that there is an interaction between mestranol and paracetamol leading to a decrease in total body paracetamol clearance.