Aspirin (ASA), in addition to blocking platelet cyclooxygenase, thus preventing thromboxane A2 formation, can also block renal cyclooxygenase thus inhibiting the renal synthesis of vasodilatory prostaglandins (PGs) which can induce renal function deterioration. The purpose of the present study was to clarify the pharmacological basis of the inhibitory effect of ASA on renal cell cyclooxygenase in the rat. ASA was given to rats either i.v. or p.o. at doses ranging from 10 to 200 mg/kg. After both i.v. and p.o. administration ASA was rapidly detected in plasma as intact molecule. The kinetics were of a dose-dependent type with a disproportionate increase in plasma level increasing the dose. Plasma salicylic acid (SA) concentrations peaked after ASA with a precursor product relationship. ASA levels in kidney homogenates were also determined after i.v. and p.o. ASA. Whereas after i.v. administration ASA was detected in the kidney as intact molecule, no ASA was detected in the kidney after p.o. administration. SA was measurable in the kidney after both i.v. and p.o. ASA with a time course which paralleled the plasma concentrations. Results of isolated kidneys perfused with a medium containing ASA and of kidney homogenates exposed to ASA "in vitro" indicate that ASA is rapidly converted to SA by kidney tissue enzymes. After ASA hydrolysis SA accumulates in the kidney and may protect renal cyclooxygenase from the inhibitor effect of ASA.