The prolonged administration of the hypocholesterolaemic drug 4-APP induced morphological changes in rat zona fasciculata cells (AER hypertrophy, peroxisome proliferation and lipid droplet depletion), enabling them to synthesise their own cholesterol and to maintain an adequate level of corticosterone output. Chronic ACTH administration provoked, in zona fasciculata cells of 4-APP-treated rats, a further increase in the AER and the volume of peroxisome compartment, coupled with a significant rise in the volume of the mitochondrial compartment and in the surface area per cell of mitochondrial cristae; the volume of the lipid droplet compartment did not change, whereas the plasma level of corticosterone significantly increased. These findings indicate that the modified adrenocortical cells of 4-APP-treated rats possess a good functional reserve, being still able to enhance their growth and steroidogenic capacity in response to ACTH. Aminoglutethimide, a drug blocking cholesterol utilisation in steroid synthesis, lowered the blood level of corticosterone in 4-APP/ACTH-administered rats; it increased the intra-adrenal concentration of cholesterol, but did not provoke lipid droplet accumulation in zona fasciculata cells. This result may suggest that in adrenal lipid droplets is stored only exogenous cholesterol taken up from plasma lipoproteins.