Although pulsatile LH release in ovariectomized (OVX) rats appears to be controlled by pulsatile discharges of LHRH, the neuroendocrine regulation of episodic FSH release remains to be explored. The main objective of the present study is to compare and contrast the effects of a potent LHRH antagonist (ALHRH) and a central nervous system depressant, phenobarbital (PhB), on pulsatile LH and FSH release in OVX rats. Three to 4 weeks after ovariectomy, blood samples were obtained at 10-min intervals for 3 h, after which LHRH was injected and sampling continued for an additional hour. In control OVX rats, periodic increases in plasma LH and FSH levels occurred approximately every 30 to 60 min, respectively. Treatment of OVX rats with PhB several hours earlier resulted in a suppression of mean plasma levels and pulse frequencies of both LH and FSH. Interestingly, PhB suppressed the pulse amplitude of LH, but not of FSH. Phenobarbital increased pituitary LH responses to LHRH, but did not alter the FSH responses. When ALHRH was given to OVX rats 24 h before blood sampling, mean plasma LH levels as well as LH pulse frequency and amplitude were severely diminished. In striking contrast, ALHRH did not affect the frequency or amplitude of FSH pulses. However, mean plasma FSH levels were suppressed to 31% of levels measured in control OVX rats. These results demonstrate that in contrast to LH secretion, FSH secretion in OVX rats appears to be regulated by two distinct neuroendocrine mechanisms: an LHRH-dependent mechanism controlling the nonepisodic component of FSH secretion (baseline secretion) and a LHRH-independent mechanism controlling pulsatile FSH release.