We used a biomimetic model system to ascertain how lignification and diverse shifts in lignin cross-linking and composition influence cell wall fermentation. Primary cell walls from nonlignified maize cell suspensions were artificially lignified with varying ratios of normal monolignols (coniferyl and sinapyl alcohols) and with normal plus unusual monolignols (5-OH coniferyl alcohol, coniferaldehyde, sinapyl acetate, and dihydroconiferyl alcohol) identified in normal, mutant, and transgenic plants. Cell walls with normal or reduced feruloylation were also lignified with varying proportions of sinapyl p-coumarate, a precursor of p-coumaroylated grass lignins. Cell wall fermentability was determined by measuring gas production during in vitro ruminal fermentation (a proven surrogate measure of fiber saccharification and fermentation to ethanol). Increasing the lignin content of cell walls from 0.5 to 124 mg/g increased lag time by 37%, decreased fermentation rate by 37%, and decreased fermentation extent by 18% from hemicelluloses. Lignification increased lag time for cellulose by 13-fold without influencing the rate or extent of fermentation . Ferulate cross-linking of xylans to lignin accounted for at least one-half of the inhibitory effects of lignin on cell wall fermentation. Copolymerizing sinapyl p-coumarate with monolignols increased the extent of hemicellulose fermentation by 5% without significantly affecting other kinetic parameters. Other shifts in the lignin composition did not alter the kinetics of fermentation. The results indicate that continued selection or engineering of plants for reduced lignification or ferulate cross-linking will improve fiber fermentability more than perturbing monolignol biosynthesis solely for the purpose of altering lignin composition.