The localization of natriuretic peptide receptors was studied in LLC-PK1 cell monolayers grown on a micro-porous membrane filter. The addition of alpha-human atrial natriuretic peptide (alpha-hANP) to the apical side of the cells produced a concentration-dependent increase in cyclic GMP (cGMP) formation, the extent of which was similar to that produced by the addition to the basolateral side. More cGMP was formed with alpha-hANP (1 and 100 nM) than with the C-type natriuretic peptide (100 nM). These findings indicate that the biologically active receptors with high efficacy for alpha-hANP are expressed in both the apical and basolateral membranes in LLC-PK1 cells.