Administration of chlordiazepoxide (CDP) (5 mg/kg) decreased plasma corticosterone (CS) levels of mice exposed to noise stress and increased CS levels in nonstressed mice (20 and 40 mg/kg). The increase in CS may be related to an observed decrease in locomotor activity. Quipazine (0.5 mg/kg), a serotonergic agonist, failed to alter CS levels in animals without prior drug treatment and attenuated the rise in CS of nonstressed mice. These results contradicted a possible serotonergic facilitatory effect on CS regulation. Administration of apomorphine (0.5 mg/kg) or clonidine (0.1 mg/kg) prevented the significant reduction of CS levels in stressed mice treated with low doses of CDP. Apomorphine, alone, increased CS of nonstressed mice to levels approximating those of vehicle-treated stressed mice. Thus, a norepinephrine inhibitory effect was not evident and possible dopaminergic involvement in CS response regulation was suggested. It seemed likely that the effect of CDP on the hypothalamic-pituitary-adrenal system was dependent upon the endocrine state of the animal. Mice exposed to stress and exhibiting higher levels of CS were affected differently by CDP treatment than their nonstressed counterparts.