The composition of the uterine fluid is of importance for the development of the embryo. The ionic composition of the uterine fluid is determined by transport processes in the uterine epithelium. The aim of the present study was to investigate whether nicotine can affect the ion transport processes and ultrastructure of the uterine epithelium in mouse and rat. The effects of nicotine on the uterine epithelium were compared with those on kidney and liver. Nicotine was administered to mice as an intraperitoneal injection of a 1 microgram/l nicotine solution twice daily for 8 days, or in the drinking water (108 microM nicotine) for 15 days, whereas rats received nicotine in their drinking water for 10 days (54 or 108 microM nicotine). In addition, primary cultures of endometrial cells were exposed to nicotine in vitro. Changes in morphology were examined by transmission electron microscopy and changes in elemental content by X-ray microanalysis. Nicotine caused a significant decrease in the concentrations of Na, K, and Cl in the uterine fluid and in the endometrial cells in situ. Similar changes in elemental concentrations were observed in endometrial cells in vitro. Ultrastructural changes in endometrial cells included swollen and damaged mitochondria. In liver and kidney much smaller effects of nicotine on the elemental composition of the cells were observed. However, marked ultrastructural effects were seen in the kidney: a reduction in mitochondrial size and an increase in lysosomal volume. It is concluded that nicotine directly interferes with fluid transport across the uterine epithelium.