We have used human kidney cortical and medullary cells in primary culture as an experimental model, in order to study the effect of prostaglandin E2 on the adenylate cyclase-cyclic AMP system at renal level, in comparison with that of parathormone and desamino 1-D-arginine 8-vasopressin. Prostaglandin E2 is a more potent stimulator of cyclic AMP accumulation in cortical cells than in medullary ones, the minimal effective dose being 3 nM in the cortex and 20 microM in the medulla. The maximal response was obtained with 30 microM in cortical cells and with 0.3 mM in medullary ones. The effects of combining submaximal and maximal active doses of the three hormones were always additive when tested on cortical cells. On the contrary, prostaglandin E2, at doses effective on the medullary cells adenylate cyclase system, produced an increase of cyclic AMP accumulation significantly lower than expected when incubated with submaximal and maximal amounts of desamino 1-D-arginine 8-vasopressin. Present data provide evidence for the existence of distinct receptors for parathormone, arginine-vasopressin and prostaglandin E2 at cortical level; the possible role of prostaglandin E2 in the counter-regulation of arginine-vasopressin action on medullary cells in unlikely, in view of the high prostaglandin E2 concentration which is necessary to exert this effect.