Signs of feminization are seen in men with cirrhosis of alcoholic but also of nonalcoholic origin even in the absence of markedly increased plasma estrogen levels. Recently identified alterations of hepatic sex hormone receptor levels have provided a hypothetical mechanism for the pathogenesis of the feminization seen in cirrhotic men. The aim of the present study was to determine the effect of experimental portal-systemic shunting in adult male rats on hepatic sex hormone receptor levels, plasma sex hormones, and two markers for sex hormone action in the liver. The following alterations were found in male rats with surgically created portacaval shunts compared with sham-operated controls: the hepatic content of cytosolic estrogen receptors was reduced by 35% and the cytosolic androgen receptors content by 59%; plasma levels of estradiol increased 6.7-fold while those of testosterone were reduced by 71%; the estrogen-responsive ceruloplasmin levels were decreased by 31% and the androgen-responsive male-specific estrogen binder by 72%. Based on these data, it can be concluded that portal-systemic shunting reduces the hepatic cytoplasmic content of several sex hormone related proteins. These changes are paralleled by a decreased estrogen responsiveness of the liver, as evidenced by the plasma ceruloplasmin level.