SPARC, a Ca(2+)-binding glycoprotein that is expressed during tissue morphogenesis and functions as an inhibitor of cell spreading in vitro, was found to induce the secretion of an Mr = 45,000 protein in bovine aortic endothelial (BAE) cells. This protein was identified as type 1 plasminogen activator inhibitor (PAI-1) on Western blots with anti-PAI-1 antiserum. SPARC stimulated the secretion of PAI-1 protein into the medium of subconfluent BAE cells, but not confluent BAE cells, in a dose- and time-dependent manner. Secretion of PAI-1 into the culture medium was progressive and exhibited an increase of 3- to 7-fold over control values within 24 h after the addition of SPARC. Levels of PAI-1 mRNA were elevated 2-fold within 4 to 24 h after the addition of SPARC and did not increase with higher concentrations of SPARC. Since the induction of PAI-1 mRNA by SPARC was not blocked by cycloheximide, de novo protein synthesis was apparently not required for this stimulation. Control experiments showed that the induction of PAI-1 was not due to contamination of the SPARC preparations with endotoxin. These data demonstrate that SPARC induces the biosynthesis of PAI-1 in BAE cells and suggest a role for SPARC in the regulation of fibrinolysis and in the control of proteolytic events in remodeling tissues.