Although activation of Th1 inflammatory pathways is a hallmark of chronic heart failure (HF), underlying changes in immune effector cells are poorly understood. Dendritic cells (DCs) are orchestrators of T-cell polarization, and thereby can regulate Th1 and Th2 responses. We hypothesized that alterations in the local and systemic DC network, and tissue DC trafficking, underlie the pro-inflammatory state in HF. Post-infarction HF was studied in adult C57BL/6 mice 8 wks following left coronary ligation; sham operated mice served as controls. Pathological remodeling and HF were verified by echocardiography, hemodynamics, gravimetry and histology. Cardiac interstitial cells were isolated by collagenase digestion of the heart followed by density gradient centrifugation; standard isolation procedures were used to isolate splenic, BM, and PB cells. We characterized two major DC subsets using flow cytometry: 1) classical DCs (cDCs, CD11c+B220-) that initiate adaptive immune responses and enhance interferon production from T cells, and 2) plasmacytoid DCs (pDCs, CD11c+B220+) that upon proper stimulation can produce pro-inflammatory cytokines that polarize T cells to a Th1 phenotype or, alternatively, suppress adaptive immunity. Compared with sham-operated mice, HF mice exhibited significantly (p < 0.05) increased cDCs in PB (3.65±0.34 vs 1.36±0.27%), spleen (3.65±0.41 vs 2.35±0.22%), and heart (4.22±0.15 vs 3.1±0.40%), but no changes in BM. A major cDC subset, CD11c+B220-CD8+ cells, preferentially endocytose dying cells and stimulate Th1 CD4+ T cell responses. In HF mice, these cDCs significantly (p < 0.01) increased in PB (0.17±0.018 vs 0.053±0.017%) and spleen (0.35±0.035 vs 0.21±0.027%). Additionally, there were significant (p < 0.05) increases in pDCs in the heart (2.55±0.44 vs 0.60±0.30%), spleen (2.32±0.40 0.90±0.11%) and BM (1.30±0.10 vs 1.02±0.08%), but no changes observed in PB as compared with sham. Hence, we conclude that in HF, there are augmented cDCs and pDCs locally in the heart and selective alterations in the PB, spleen, and BM that together support the development of systemic Th1 responses. A better understanding of DC networks in HF can elucidate the mechanisms of pathological inflammation and lead to novel therapeutic approaches.