Atriopeptins are a recently-discovered group of polypeptides secreted from cardiac myocytes in response to fluid overload. The present studies demonstrate that atriopeptin receptors, coupled to the activation of guanylate cyclase, are present in rabbit ciliary process. Rat atrial natriuretic peptide 1-28 (rANP) activated ciliary process guanylate cyclase activity with a Vmax of from 24-337% and with a Ka of from 0.4-4 nM, similar to that for atriopeptin receptors present in rabbit kidney. Activation was greater for the intact peptide than for rANP fragments 1-11 or 13-28, and stimulated activity was greater in isolated ciliary processes than in ciliary muscle or iris. Intravitreal injection of the complete peptide into living rabbits caused a marked decrease in IOP in the ipsilateral eye which persisted for more than 48 hr and occurred without evidence of an inflammatory response. There was a smaller decrease in IOP in the contralateral eye. Following intravitreal injection of rANP 1-28, atriopeptin levels in aqueous humor remained elevated for at least 44 hr. Injection of the biochemically less active rANP fragments 1-11 and 13-28 caused no decrease in IOP. These physiological data, together with the biochemical identification of atriopeptin receptors and second messenger systems in the ciliary process, suggest that certain tissues of the anterior segment may be atriopeptin end-organs and that agents acting at atriopeptin receptors may be able to regulate IOP.