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Plasminogen is a hemostasis-related phenotype and is commonly implicated in thrombotic and bleeding disorders. In the San Antonio Family Heart Study (SAFHS), we performed to our knowledge the first genomewide linkage scan for quantitative trait loci (QTLs) that influence the level of plasminogen. The subset of the SAFHS population used for this study consists of 629 individuals distributed across 26 extended Mexican American families. Pedigree-based variance component linkage analyses were performed using SOLAR. The mean plasminogen level was 114.94%±17.8 (range, 42–195). The heritability (h2) of plasminogen was 0.43±0.08 ( p < 6.3×10–13). One region on chromosome 12 (12q14.1) showed suggestive evidence of linkage (LOD = 2.73, nominal p < 0.0002, genomewide p = 0.0786) near marker D12S1609. Because plasminogen has important effects in many human health problems, such as cancer and atherosclerosis, the role of this putative QTL in the regulation of plasminogen variability needs to be studied further.