Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender-matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation.