The production of mouse serum amyloid P component (SAP), a major acute phase protein of liver origin, was studied immunocytochemically using the peroxidase staining technique. SAP was not detectable in the cytoplasm of hepatocytes from normal, unstimulated mice, nor was it observed before 24 h after an acute phase stimulus. 125I-labelled mouse SAP was cleared from the plasma in vivo with a half-life of 7.0-8.25 h in all animals studied including: normal mice of different strains with different genetically determined plasma SAP concentrations; mice undergoing acute phase responses with greatly elevated plasma SAP levels and mice with casein-induced amyloidosis. The circulating level of SAP is thus independent of its rate of clearance and catabolism and is determined by the rate of synthesis and/or secretion of SAP.