Patients suffering from AIDS tend to have symptoms that resemble those encountered in adrenocortical insufficiency. Serum sodium concentrations and blood pressure values were monitored and found to be subnormal, despite the fact that renin activity and aldosterone levels were either normal or elevated. We report the presence of autoantibodies directed against hydrocortisone among such AIDS patients. Indirect immunofluorescence technique using patients' sera and adrenal glands from AIDS patients as antigen showed antibodies to adrenocortical cells in sera from 9 of the 12 AIDS patients and in none from patients with autoimmune diseases and viral diseases or healthy blood donors. No similar reaction was seen in normal human or monkey adrenal glands. An ELISA technique was developed using hydrocortisone as antigen and using this technique 45% of the AIDS patients were found to have antibodies to hydrocortisone. It is possible that anti-corticosteroid antibodies (ACSA) may play a role in the pathophysiology of the Addison's like syndrome seen in terminal phases of AIDS.