OBJECTIVES/SPECIFIC AIMS: Our objective was to examine serum E2 levels in dcSSc males in relation to disease characteristics (i.e autoanitbody profile and internal organ involvement) and its impact on survival. METHODS/STUDY POPULATION: We measured serum E2 levels in 83 dcSSc men >50 years old from the University of Pittsburgh Scleroderma Center and healthy controls of similar age. Using statistical modeling, we examined the associations between circulating E2 levels, internal organ involvement, autoantibody profiles, and survival. RESULTS/ANTICIPATED RESULTS: Male dcSSc patients had significantly higher serum E2 levels compared to healthy male controls and compared to dcSSc post-menopausal women of similar age. Male dcSSc patients with high serum E2 levels had significantly more heart involvement and worse survival. Using Cox regression modeling for risk of death, increasing serum E2 levels in anti-Scl-70 antibody positive dcSSc males were associated an increased risk of death. DISCUSSION/SIGNIFICANCE OF IMPACT: DcSSc male patients have higher levels of E2 compared to healthy controls and dcSSc postmenopausal women. Elevated serum E2 levels in dcSSc males >50 are associated with heart involvement and, if anti-Scl-70 antibody positive, worse survival. Our current study expands on our previous work, not only that that E2 exerts pro-fibrotic effects on skin, but also internal organ involvement, overall survival. These data suggest an important role of estrogen imbalance in SSc.