['This study examined the role of age, gender, and disease in the regulation of the pituitary-adrenal axis.', 'Serum cortisol and immunoreactive corticotropin (ACTH) were measured for five hours after a bolus administration of ovine corticotropin releasing hormone (oCRH, 1 microgram/kg) during three separate investigations: 1) age: comparison was made between young men (26 +/- 3 years [means +/- SE]) vs old men (73 +/- 2 years); 2) gender: comparison between old men (73 +/- 2 years) vs old women (68 +/- 3 years); and 3) disease: comparison was made between healthy subjects (no disease, 44 +/- 6 years) vs subjects with a chronic stable disease (diabetes mellitus [DM] or hypertension [HBP], 48 +/- 5 years).', 'Basal concentrations of cortisol were significantly higher in younger men (127 +/- 17 vs 74 +/- 11 nmol/L, p < .03), as were peak cortisol levels (499 +/- 30 vs 397 +/- 36 nmol/L, p < .05, ANOVA). However, the 5-hour nadir of cortisol, area under the curve, delta area under the curve, time to peak, and variability of the responses during three separate admissions were similar in young and old. When the responses to oCRH in old men and old women were compared, old women had significantly higher basal values of cortisol (163 +/- 30 vs 75 +/- 11 nmol/L, p < .02), peak levels of cortisol (p < .0001) and the 5-hour nadir of cortisol was 124% higher in older women (657 +/- 61 vs 298 +/- 50 nmol/L, p < .0006). When the response to oCRH was examined in healthy subjects and subjects with disease (DM and HBP), men with disease had a peak cortisol response 40% higher (p < .003) than healthy men and the level remained 85% higher (p < .0005) at 5 hours. The responses of ACTH to oCRH were not different in the groups being compared for any study. The variation of cortisol response could be explained by the peak cortisol levels (R2 = .718, p < .0001), with a small significant contribution from disease (R2 = .013, p < .002). In summary, the adrenal response to oCRH remained elevated throughout the period of study in elderly women. In addition, subjects with a chronic disease (DM and HBP) had a greater response of cortisol to oCRH compared with healthy subjects.'] Is the pituitary-adrenal glucocorticoid response altered by gender and disease?