In the stress-induced hyperthermia (SIH) paradigm in mice, both a benzodiazepine receptor agonist, diazepam, and a 5-HT1A receptor agonist, flesinoxan, reduced the stress-induced increase in rectal temperature. The SIH procedure itself enhanced plasma ACTH and corticosterone levels but not plasma glucose levels. Diazepam (3, 6, and 12 mg/kg p.o.) did neither affect basal plasma ACTH, corticosterone, or glucose levels, nor did it suppress the stress-induced rises in these parameters. Flesinoxan (1, 3, and 10 mg/kg p.o.) enhanced plasma ACTH and corticosterone concentrations under nonstress conditions but did not affect the stress-induced increases in ACTH and corticosterone secretion. No clear effects of flesinoxan on plasma glucose levels were found. Our results indicate that in mice the anxiolytic effects of diazepam and flesinoxan in the SIH paradigm are not paralleled by a blockade of stress-induced increases in plasma ACTH, corticosterone, and glucose levels.