The effects of a prolonged treatment with vasoactive intestinal peptide (VIP) on the morphology and hormone secretion of the rat adrenal gland were investigated. VIP administration caused a significant hypertrophy of the Zona glomerulosa and its parenchymal cells, coupled with a notable rise in the blood level of aldosterone. Zona fasciculata morphology and the blood concentration of corticosterone were not affected. Plasma potassium concentration, the level of circulating ACTH and plasma renin activity did not display any significant variation in VIP-treated animals. The possibility is discussed that VIP may be specifically and directly involved in the control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa. I Some investigations demonstrated the existence of a VIP-ergic innervation in the rat adrenal zona glomerulosa (9, 10) and ovary (1). Moreover, vasoactive intestinal peptide (VIP) was reported to stimulate steroid secretion by murine Y-1 cell line (12, 19) and frog interrenal cells (13, 14), as well as by cultured rat granulosa cells (2). Previous studies failed to show any effect of VIP on aldosterone secretion by isolated rat zona glomerulosa cells (4), but recently some of us demonstrated a clear-out acute effect of this peptide in vivo (23). Many lines of evidence have stressed the multifactorial regulation of zona glomerulosa growth: in addition to ACTH, K+ and angiotensin II (see 21, for reference), somatostatin (17, 24), prolactin (18), a-MSH (27) and methionine-enkephalin (26) seem to be involved. It therefore seemed worthwhile to investigate the effect of a prolonged administration of VIP on the morphology and function of rat adrenal Zona glomerulosa.