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Silky windgrass is a serious weed in central and northern Europe. Its importance has escalated in recent years because of its growing resistance to acetolactate synthase (ALS)-inhibiting herbicides. This study investigated the resistance level for three herbicide sites of action in eight silky windgrass populations, collected in fields neighboring a field where iodosulfuron sodium salt–resistant silky windgrass had previously been found. Target site resistance (TSR) and non–target site resistance (NTSR) mechanisms were identified, and a spatial gradient distribution hypothesis of ALS resistance was tested. Populations showed large variations in ED50values to iodosulfuron, with resistance indices (RIs) ranging from 0.1 to 372. No cross-resistance was found to other herbicide groups with the same site of action as iodosulfuron. In contrast, resistance was observed to the acetyl-CoA carboxylase inhibitor, fenoxaprop ethyl ester (RI from 0.7 to 776), while the activity of prosulfocarb, an inhibitor of long-chain fatty-acid synthesis, was unaffected. Iodosulfuron-resistant phenotypes were associated with NTSR, while fenoxaprop ethyl ester resistance was caused by both NTSR and TSR (Ile-1781-Leu mutation). A large-scale trend in the spatial distribution of resistance to ALS indicated a decreasing resistance with increased distance from an epicenter. After finer-scale analysis, less than 0.05% of the residual variation could be attributed to spatial autocorrelation. The spatial resistance pattern was not correlated with the dominant wind direction, while there was a correlation between the resistant phenotype and type of crop. This study underlines that NTSR mechanisms do not always confer broad resistance to different herbicide subclasses and site of action, hence the complex relationship to resistant phenotype. NTSR mechanisms, in particular detoxification, were present at different levels for the herbicides tested in the silky windgrass populations of this study. The factors contributing to the spatial distribution of resistance remain elusive.