Previous studies in our laboratory support the notion that an increase in the production of cyclic AMP (cAMP) by the kidney may play a role in the natriuresis of extracellular fluid volume expansion (ECVE). The present study was designed to evaluate whether a suppression in the rise in nephrogenous cAMP is involved in the blunted natriuretic response to ECVE during acute caval constriction. ECVE was produced by saline infusion in 8 thyropara-thyroidectomized dogs during acute constriction of the thoracic inferior vena cava and after its release. Arterial pressure decreased during caval constriction and ECVE and returned to values not different from control after the release of the constriction. There were no significant changes in renal plasma flow, glomerular filtration rate (GFR), fraction of filtered sodium excreted, or nephrogenous cAMP during the caval constriction. The release of the constriction in 4 dogs was followed by no significant changes in renal plasma flow and GFR, while the fraction of filtered sodium excreted increased significantly together with a significant rise in total nephrogenous cAMP by 1,682 ± 409 pmol/min (p < 0.05). The data are consistent with the hypothesis that the blunted natriuresis during ECVE in caval dogs is at least partly due to lack of increment in nephrogenous cAMP. The results provide further support for the role of renal cAMP in modulating renal handling of sodium.