ATRIAL natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation¹. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator of the physiological effects of the hormone^2,3. Guanylate cyclase exists in at least two different molecular forms: a soluble haem-containing enzyme consisting of two summits^4,5 and a non-haem-containing transmembrane protein having a single subunit⁶. It is the membrane form of guanylate cyclase that is activated following binding of ANP to target cells^3,7,8. We report here the isolation, sequence and expression of a complementary DNA clone encoding the membrane form of guanylate cyclase from rat brain. Transfec-tion of this cDNA into cultured mammalian cells results in expression of guanylate cyclase activity and ANP-binding activity. The ANP receptor/guanylate cyclase represents a new class of mammalian cell-surface receptors which contain an extracellular ligand-binding domain and an intracellular guanylate cyclase catalytic domain.