The effects of ANF (99-126) and its active analog, [3-mercaptopropionic 105]-ANF (105-126), on diuresis and natriuresis were assessed in the rat after intramuscular (i.m.) or subcutaneous (s.c.) injection. Water and sodium excretion increased significantly after i.m. or s.c. administration of either peptide in the first 20-min urine collection. ANF (99-126) was more active i.m. than its analog, while they both produced similar diuresis and natriuresis when they were administered s.c. The rapid and significant increase of plasma IR-ANF levels, detected by radioimmunoassay and analyzed by high performance liquid chromatography after i.m. or s.c. injection of these peptides, indicates very rapid passage into the blood circulation without degradation. These data demonstrate that either the i.m. or s.c. route can be used to administer ANF or its analog.