The degenerative responses of luteinizing hormone-releasing hormone (LHRH)-containing neurons within the mediobasal hypothalamus (MBH) after knife cut lesions (FC) made in the frontal plane of the retrochiasmatic hypothalamus include a reduced number of LHRH-immunoreactive (ir) nerve terminals in the median eminence, reduction in LHRH content of the MBH and growth of novel irLHRH-containing neural processes into FC scar tissue. We have now investigated basal and secretogogue-evoked LHRH release in vitro from the preoptic area-MBH (POA-MBH) of adult male rats at 10 or 60 days after FC. Basal LHRH release rate (P < 0.05) and total (P < 0.01) amount released 60 days after FC were reduced when compared to control (CONT) hypothalami, but not slams. A 30 min pulse of naloxone (NAL, 1 mg/ml) stimulated >2-fold relative increase in LHRH release for all groups; however, the total amount of LHRH released by FC hypothalami was less (P < 0.05) than that of CONT, but not sham POA-MBHs. Although exposure to elevated KCl significantly increased (P < 0.01) LHRH release for all 3 groups, the FC secretory response was less than that of both CONT (P < 0.05) and sham (P < 0.01) groups. In the second experiment single POA-MBH were perifused at 10 days (sham and FC) or 60 days (CONT, sham and FC) after surgery. Basal LHRH secretion rates at 10 days after FC were reduced to 42% and to 68% at 60 days after surgery (P < 0.05 vs sham POA-MBH) and again KCl-evoked LHRH released was significantly lower from the POA-MBHs of both groups of FC rats. LHRH concentrations in tissue samples at the end of 6 h perifusion were also lower after FC at both 10 and 60 days and there was a positive linear correlation (P < 0.01) between individual concentrations and basal release rates. In summary, partial surgical interruption of the preoptico-tuberal pathways results in a persistent, significant reduction in the POA-MBH LHRH concentration, as well as basal and secretogogue evoked release rates. Thus, any regenerative, novel LHRH-containing nerve terminals that may appear in the POA-MBH after surgical axotomy do not result in a significant improvement in LHRH secretion or concentration.