Cell proliferation and programmed cell death play important roles in the maintenance of tissue dynamics. The adrenal cortex has been known as a cell renewal tissue. We studied cell proliferation by Ki67 immunostaining and programmed cell death or apoptosis by a recently developed 3'-OH nick end labeling technique. Fifteen cases of normal human adrenal; 22 cases of adrenocortical adenoma including Cushing's adenoma (five cases), aldosteronoma (nine cases), and nonfunctioning adenoma (eight cases); and six cases of adrenocortical carcinoma were examined. In normal adrenal cortex, Ki67 immunoreactivity was predominantly observed in the zona fasciculata in all the cases examined, whereas cortical cells positive for nick end labeling were present in the zona reticularis in all cases and in the zona glomerulosa in five cases. These results suggest that the "cell migration" or "centripetal" theory is also applicable in cell turnover of normal human adrenal cortex, and cortical cells may move in two directions, from fasciculata to reticularis and from fasciculata to glomerulosa in some instances. CD68-positive sinusoidal lining cells, which are considered to ingest the cells undergoing apoptosis, were present throughout the cortex. In adrenocortical adenoma, Ki67 immunoreactivity was observed in all cases, and tumor cells positive for nick end labeling were observed in 12 cases (Cushing's adenoma in three cases, aldosteronoma in four cases, and nonfunctioning adenoma in five cases). In adrenocortical carcinoma, Ki67 immunoreactivity was observed in all the cases, and its labeling index was significantly higher than that of normal adrenal and adrenocortical adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)