In 24 conscious newborn piglets the effects of 20 μg/kg body weight IV 1-deamino-8-d-arginine-vasopressin (DDAVP) in group 1,5 mg/kg PO indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate, urinary osmolatity, creatinine clearance, total urinary and nephrogenous cyclic-adenosine 3':5'-monophosphate (cAMP) excretion, medullary cAMP content, and renal prostaglandin (PG)E2and PGF20, excretion. DDAVP alone had no significant effects on the above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly (urinary flow rate decreased from 2.4 × 0.4 to 1.4 × 0.3 ml/hr (means × S.E.), and urinary osmolality increased from 444 × 29 to 552 × 33 mOsm/liter). Total urinary and nephrogenous cAMP excretion increased from 590 × 48 to 854 × 78 and 302 × 36 to 590 × 81 pmoles/hr/g kidney weight, respectively, whereas PGE2and PGF20decreased from 249 × 33 to 19 × 4 and 192 × 32 to 43 × 7 pg/hr/g kidney weight, respectively. In addition, medullary cAMP content was considerably higher in group 3 (2010 × 200 pmoles/g medulla) than that observed in the control (1187 × 137), DDAVP (1218 × 115), and indomethacin (1230 × 168) groups.