The present study in rats evaluated the concept that a humoral factor regulates opsonic fibronectin levels. Intravenous administration of gelatin-coated particles depletes immunoreactive opsonic fibronectin by 95% within 30 minutes. Partial restoration of opsonic protein was observed by 3 hours with complete recovery 6-24 hours. Post-blockade serum was then evaluated with respect to this humoral factor. Controls were given either normal serum or serum rendered fibronectin-deficient by affinity chromatography. Affinity-adsorbed fibronectin-deficient serum did not increase immunoreactive opsonic fibronectin. Injection of normal serum resulted in the expected elevation in fibronectin due to its fibronectin content. In contrast, injection of fibronectin-deficient serum obtained during RE blockade dramatically elevated (P less than 0.02) immunoreactive opsonic fibronectin to 160.6 +/- 14% of control levels by 3 hours. Thereafter, fibronectin levels returned to control over the 6-24 hour period. Our temporal studies suggest that a circulating transferable factor, which may be a hormone, may influence the synthesis and/or release of opsonic fibronectin.