One day of fasting suppresses pulsatile LH secretion in adult male rhesus monkeys. In the present study, we determined whether the hypothalamic-pituitary-adrenal (HPA) axis is activated by 1 day of fasting, and if there is any evidence that an increase in the activity of the HPA axis causes the fasting-induced suppression of LH secretion. In the first experiment, blood samples were collected at 15-min intervals from nine monkeys for 24 h (0800-0800 h) on a day of normal feeding (animals fed a single daily meal at 1100 h) and again on a day of fasting (animals not fed their daily meal) to assess changes in LH and cortisol secretion caused by fasting. LH secretion on the day of fasting (4.44 +/- 0.85 LH pulses/24 h) was significantly suppressed compared to that on a day of normal feeding (7.67 +/- 0.74 LH pulses/24 h; P < or = 0.01), and there was a slight, but significant, rise in plasma cortisol levels from 17.86 +/- 2.29 to 25.14 +/- 2.74 micrograms/dl (measured at 1400 h) that was evident soon after the meal was missed on the day of fasting. However, within individual animals, there was no correlation between the rise in plasma cortisol levels and the decrease in LH secretion observed on a day of fasting (r = 0.37). A second experiment was performed to determine whether the small rise in plasma cortisol levels that occurred on a day of fasting was capable of suppressing LH secretion. Hydrocortisone acetate (HCA) was administered to six normally fed monkeys, creating a rise in plasma cortisol levels somewhat greater than the levels occurring during fasting (HCA treatment, 44.51 +/- 1.48 micrograms/dl; fasting, 18.42 +/- 1.62 micrograms/dl; measured between 1100-2400 h). However, HCA treatment had no effect on LH secretion, suggesting that the rise in cortisol that occurs during fasting does not cause LH suppression. To determine whether increased secretion of the neuropeptides that provide the central drive to the adrenal axis causes the suppression of LH secretion during fasting, six animals were treated with dexamethasone (0.25 mg/kg, im) on a day of fasting to inhibit the activity of the glucocorticoid-sensitive CRH neurons of the adrenal axis via increased glucocorticoid negative feedback. Dexamethasone treatment caused a marked suppression of circulating cortisol levels (to approximately 1.0 micrograms/dl), but it did not prevent the fasting-induced suppression of pulsatile LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)