Adenohypophysis, neural lobe, stalk, and median eminence are interconnected by capillary networks and portal vessels, but the directions of blood flow are not clearly understood. To test the hypothesis that peptides released from the hypothalamohypophysial tract (HHT) may reach the adenohypophysis, the HHT of anesthetized rats were stimulated electrically with 5-s trains of constant current (400 microA) biphasic impulses (0.2-1 ms) at 30 Hz, and extracellular potassium activity was recorded in various parts of the hypothalamohypophysial complex with microelectrodes (2- to 4-micrometer tip). Within HHT and neural lobe, K+ increased without delay (within 30 ms) from 2.20 +/- 0.25 (meq/l, mean +/- SE) and 2.65 +/- 0.40 to 4.50 +/- 0.60 and 7.60 +/- 0.85, respectively. Within the anterior dorsal regions of the adenohypophysis (AAH), K+ increased from 3.00 +/- 0.25 to 5.05 +/- 0.35, but with a delay of 1-4 s. Within the posterior regions of the dorsal adenohypophysis, the increase was barely significant (P < 0.1) and was delayed by 4-10 s. K+ responses in AAH to nicotine and HHT stimulation were abolished by circulatory arrest; thus K+ responses were not due to current spread or passive diffusion. Coagulation of long portal vessels did not diminish K+ responses in AHH. Results suggest that peptides released from HHT are not only secreted into the general circulation, but may reach the adenohypophysis through a portal vascular route.