Although they possess significant viticultural advantages, interspecific hybrid grapes (Vitis spp.) are reported to produce wine with lower tannin concentrations than European wine varieties (Vitis vinifera). However, extensive quantitative data on this phenomenon as well as mechanistic explanations for these differences are lacking. A survey of primarily commercial wines from the Finger Lakes American Viticultural Area (New York) using a protein precipitation method determined that hybrid-based wines had >4-fold lower tannin concentrations than vinifera wines. To elucidate factors responsible for differences in wine tannin, 24 wines were produced from both red hybrid and vinifera cultivars under identical conditions. Lower wine tannin in French-American hybrid- than vinifera-based wines could be partially explained by lower grape tannin. However, experiments in which cell wall material was incubated with tannin indicated that cell wall binding may be of equal or greater importance in explaining lower wine tannin concentrations in hybrid-based wines. Subsequent characterization of cell wall material revealed that protein in flesh cell walls and, to a lesser extent, pectin in skin cell walls were correlated with cell wall binding.