We examined the possibility that alterations in the timing of cyclic luteinizing hormone (LH) release during the middle age transition to infertility reflect differences in the circadian pattern of neural function in pacemaker areas of the hypothalamus, particularly the suprachiasmatic nucleus. We measured local cerebral glucose utilization (LCGU) because this parameter is an index of local brain function. We assessed LCGU in several brain areas of young and middle-aged ovariectomized estradiol-treated rats since LH surges are altered when rats are middle-aged. This alteration is correlated with changes in the diurnal pattern of neurotransmitter turnover in several hypothalamic areas that regulate cyclic LH release. The data demonstrate a circadian rhythm in glucose utilization in the dorsal and ventral suprachiasmatic nucleus. In young rats, LCGU increases within 1 hr of lights-on, increases further just prior to the initiation of the LH surge, and decreases within 1 hr of lights-off. In contrast, middle-aged rats show a more gradual increase in LCGU after lights-on, with no further increase prior to the LH surge, and a premature decrease during the afternoon and evening. The data suggest that changes in the circadian pattern of LCGU may be related to the alteration in timing and amplitude of estradiol-induced LH surges in middle-aged rats. Changes in the integrity of the biological clock or in the ability of the biological clock to entrain other neurochemical events may underlie the onset of altered cyclic reproductive function and the transition to irregular estrous cyclicity.