Although they possess significant viticultural advantages, interspecific hybrid grapes (Vitis spp.) are reported to produce wine with lower condensed tannin (CT) concentrations than premium European wine varieties (V. vinifera ). To elucidate the factors responsible, wines were produced from both red hybrid and vinifera cultivars under identical conditions in the Finger Lakes American Viticultural Area (AVA). Wine CT quantities varied across cultivars by up to 17 fold, while fruit CT differed by only up to 6 fold. CT in wines produced from V. vinifera grapes were an order of magnitude higher those in hybrid species (<50 mg/L), but lower than average CT values reported for US West Coast wines, 255 vs 544 mg/L. Further experiments in which cell wall material was incubated with CT indicated that CT binding to cell wall material may be of greater importance than grape CT for explaining wine CT variation. Cell wall characterization revealed that protein in flesh and, to a lesser extent, pectin in skin cell walls were correlated with CT binding (r2=0.597 and r2=0.255, respectively). CT retention in finished wines was investigated by adding purified CT to native Vitis, hybrid and vinifera wines, leading to a precipitate with high nitrogen content. Proteomic analysis of the CT precipitate identified several classes of pathogenesis-related (PR) proteins. Protein concentration in juices and red wines were quantitated by SDS-PAGE and were highest in native Vitis spp. (juice= 706 mg/L, wine=296 mg/L), followed by interspecific hybrids (juice= 176 mg/L, wine=92 mg/L) and Vitis vinifera (juice = 146 mg/L, wine=16 mg/L). The fining of added CT by wine protein was modeled by the Freundlich equation (r2=0.605). To evaluate the role of grape-derived proteins in limiting CT extractability, V. vinifera and interspecific hybrids from both hot and cool climates were vinified under controlled conditions. Final CT concentration in wine was well modeled from initial grape tannin and juice protein concentrations using the Freundlich equation (r2 = 0.686). In follow-up experiments, pre-fermentation removal of juice protein by bentonite increased wine CT, suggesting that this treatment may be a viable way to increase CT extractability.