Superfusion of isolated rat adrenal glomerulosa cells for 6 h with a medium containing 2.5 nM angiotensin II (AII) reduces the aldosterone response to AII, corticotropin and potassium. Here we report that under such conditions there is a decrease in the capacity of the cells to form inositol phosphates in response to a subsequent stimulation with AII. The capacity to convert corticosterone to aldosterone is also reduced by a prior exposure to AII. Superfusion with a high-potassium medium has no such an effect. Reduced phosphoinositide response may be responsible for the decreased aldosterone stimulation by AII, the inhibition of the late stage of aldosterone biosynthesis may account for the heterologous character of desensitization.