We have previously reported that luteinizing hormone releasing hormone (LH-RH) levels in the medial basal hypothalamus (MBH) of adult male rats castrated for 2 weeks can be raised by testosterone (T) or estradiol (E2) treatment for 3-4 days. The present study was undertaken to determine the time after castration when the hypothalamus becomes refractory to this feedback action and whether prolongation of exposure to steroids would reinstate the hypothalamic LH-RH response. Treatment with T (Silastic capsules, s.c.) for 4 days, when commenced either immediately or 14 days after castration, significantly raised the MBH LH-RH levels. A 4-day regimen of E2 or dihydrotestosterone, on the other hand, evoked similar increase when commenced up to 21-28 days after castration. Further delay in institution of the 4-day treatment rendered the three steroids completely ineffective. When the effects of prolongation of treatment were tested in long-term castrated rats (56 days), it was found that T required 14 days as compared to 7 days of exposure with E2 or dihydrotestosterone to produce an equivalent MBH LH-RH response. Furthermore, the MBH LH-RH and serum LH responses were not always correlated, since increments in the MBH LH-RH were observed when serum LH levels were suppressed by physiological levels of T or dihydrotestosterone and also when they were unchanged with low levels of T or E2. These studies show that long-term castration causes a dichotomy in responsiveness of the hypothalamo-pituitary axis to steroids.(ABSTRACT TRUNCATED AT 250 WORDS)