The present study was undertaken to investigate the effect of angiotensin II (AngII) on the concentration of inositol- 1,4,5-trisphosphate (IP3) and the modulation of AngII action by estradiol in the brain. Our studies were conducted in male rat anterior pituitary, hypothalamus and cerebral cortex with and without previous estradiol treatment. In the cerebral cortex, there were no changes in IP3 content after exposure to AngII. In the anterior pituitary, AngII increased the IP3 concentration at all doses studied. However, in the hypothalamus, AngII decreased the IP3 concentration and its effect was also time dependent. Prior treatment with estradiol intensified the effects of AngII action-on IP3 concentrations, in both the pituitary (increase) and hypothalamus (decrease). These results indicate that in the male rat anterior pituitary, AngII increases phosphatidiloinositol hydrolysis, leading to the increased production of the intracellular messenger, IP3. The decrease of IP3 concentration observed in the hypothalamus suggests a different site of Angll action in this region. We also suggest that estrogens can modulate AngII action in the brain.