Administration of a large dose of atrial natriuretic peptide is associated with an increase in glomerular filtration rate, diuresis and natriuresis in normal-sodium rats. However, glomerular hyperfiltration induced by atrial natriuretic peptide is markedly decreased in low-sodium rats. Glomerular insensitivity to atrial natriuretic peptide may be due to increased activity of the renin-angiotensin system in low-sodium rats and to an accompanying hypersensitivity to adenosine. The results indicate that attenuated glomerular responses to atrial natriuretic peptide are restored by the administration of adenosine deaminase in low-sodium rats. Moreover atrial natriuretic peptide markedly increases the urinary excretion of adenosine deaminase, which may be due to increased permeability of glomeruli to the enzyme.