Taproot decline (TRD) of soybean [Glycine max (L) Merr.] is an emerging disease caused by Xylaria necrophora, and currently observed in the southern United States. X. necrophora infects soybean roots, causing necrosis and foliar interveinal chlorosis followed by necrosis. The most recent estimates of yield losses associated with this disease (0.57 - 1.18 million bushels) highlight its potential to become a major problem for producers in the region. The mechanism by which X. necrophora affects soybean remains unknown, but a plausible explanation is that phytotoxic secondary metabolites (SMs) are produced by X. necrophora in the roots. To test this hypothesis, cell-free culture filtrates (CFCFs) from three X. necrophora strains and one putative Colletotrichum siamense were used to challenge soybean stem cuttings to determine if foliar symptoms of TRD are caused by SMs, tolerance to SMs among potentially resistant soybean cultivars identified in greenhouse and field experiments, and specificity of SMs across plant species (cotton, peanut, tomato, and soybean). Measurements of chlorophyll content and root length were obtained at 7 and 14 days of exposure (DOE). Lower chlorophyll content and shorter roots were observed on all soybean cultivars treated with CFCFs of pathogenic isolates and no effects on other plant species were observed, suggesting X. necrophora produces SMs that are detrimental to soybean exclusively and resistance upon direct exposure to SMs does not exist. These results suggest soybean-specific SMs are produced by X. necrophora in the roots causing the interveinal chlorosis and subsequent necrosis observed on plants affected by TRD.