Estrogen (E) and progesterone (P) are usually used in combination for the preparation of many contraceptive formulations. As these hormones are mainly metabolized in liver and due to their intimate relationship to the immune system, the present work was done to declare their effect on the liver and spleen in non-lactating rats. The results show that injection of a combination of both hormones in a dose of 90 (E) and 450 (P) ug/200 gm body weight in non-lactating female albino rats results in several morphological changes both in liver and spleen. After 7 days of injection, the liver developed focal changes in some lobules, dilatation of blood sinusoids and slight fibrosis of portal areas. At 21 daysو a marked cellular infiltration around the blood sinusoids and in the portal areas were observed. Depletion of glycogen and increase in DNA content was noticed in hepatocytes. On the other hand; the spleen showed marked changes in lymphoid elements both in the red and the white pulp.