ABSTRACT. The aim of this study was to determine whether the thickness of the adrenocortical zone is associated with age in virgin and parous female DDD mice. The zona reticularis and zona glomerulosa of parous mice tended to be thicker than those of virgin mice at all ages. The zona fasciculata lactating parous mice was significantly thicker than that of virgin mice at 20 weeks of age (P<0.01). Age did not affect the thickness of the three outer adrenocortical zones in either group. However, in virgin mice, the X zone consisted of vacuolated and nonvacuolated cells at 5 weeks of age and only of vacuolated cells at 10 weeks of age; the number of vacuolated cells and the thickness of the zone decreased at 40 weeks of age. In contrast, parous mice of all ages lacked an X zone. The decrease in X zone thickness with age was most evident when expressed relative to organ weight. In conclusion, the thickness of the outer three adrenocortical zones is affected by endocrine changes associated with pregnancy and lactation but not by age. The thickness of the X zone is an index of growth and maturation in nulliparous female DDD mice less than one year of age. KEY WORDS: adrenal cortex, age, DDD mouse, reproduction, X zone morphology.The adrenal cortex of most mammals consists of three zones. These zones play distinct roles in steroid hormone production [11]. The mineral corticoid of the zona glomerulosa regulates Na-K valance. The glucocorticoid of the zona fasciculata regulates multiple physiological metabolisms, and the adrenal androgen is mainly produced in the zona reticularis (exclude mice and rats [11]). In the mouse, a fourth zone, the X zone, is present in the innermost cortex of the adrenal. Masui and Tamura first described the characteristics of this zone in 1924 [12]. It was named the X zone by Howard-Miller in 1927 [8]. Many studies have shown that degeneration of this zone is induced by pregnancy and lactation [10]. Furthermore, in the absence of pregnancy, X zone degeneration is induced by the administration of androgen [6]. In male mice, degeneration of the X zone is induced by sexual maturation [3]; and regeneration of a second X zone is induced by castration of adult mice or androgen administration [4,7]. Thus, the endocrinological characteristics of these four adrenocortical zones are well known. But, little studies have been conducted on agerelated changes in the morphology of these adrenocortical zones [1].Strain differences in the morphology of X zone degeneration have been observed between A/Cam and CBA/FaCam mice [15], C57BL/6By and BALB/cBy mice [8], C57BL/ 6JJms and DDD mice [18], and A/J and SM/J mice [19,20].The main differences between strains involve the extent of vacuolation, which is an index of tissue lipid content [15,18,20,24]. Although it was recently reported that the agouti locus affects vacuolation [16,19], no statistical data were provided. As female DDD mice have a thicker and more vacuolated X zone than other strains of mice [18], we considered that the female DDD mice were suitable...