BACKGROUND Bisphenol-A (BPA) is an industrial chemical, used to manufacture polycarbonate and numerous plastic articles. It has been found to cause biological effects, mimic that of oestrogen. It belongs to a group of chemicals termed "endocrine disruptors" able to disrupt the chemical messenger system in the body. Aim of the study was to demonstrate the biological effects of BPA on the vagina of female rats, with the prediction of the neoplastic changes in relation to its potential impact. MATERIALS AND METHODS Sprague-Dawley gravid dams were divided into three groups (10 per group): G1 - control group had an equivalent volume of sesame oil to that taken in the treated groups, G2 - group was administered by gavage 0.1 mg BPA/kg body weight (low-dose group) per day, and G3 - group was administered 50 mg BPA/kg body weight (high-dose group) per day, dissolved in sesame oil. Treatment was carried out on gestation days 10 through 20. The female offsprings of each group were weaned at day 21 and the vagina was dissected when became 3 months old for histological, immunohistochemical analysis (for detection of oestrogen receptors a [ERa], and the proliferation marker Ki-67), and ultrastructural study. RESULTS The low dose group showed degeneration of the epithelial lining with focal patches of decreased epithelial layers. The high dose group revealed cytoplasmic hydropic degeneration, and the pyknotic nuclei of epithelial cells. Oestrogen receptors demonstrated a significant decrease of positive cells in low dose treated group and this decrease markedly accentuated in the high dose one. Positive nuclei for Ki-67 were markedly increased with increasing doses of BPA. Electron microscopic study revealed cytoplasmic degeneration, vacuolation and mitochondrial degeneration in both treated groups. CONCLUSIONS BPA showed an obvious mix of degenerative and proliferative histological changes and clear damage of the cellular organelles. This stressful condition may predispose to neoplastic changes of the vagina.