The response of two populations (CC1, 43.59°N & 20.40°E; CC2, 44.46°N & 20.17°E) of common cocklebur ( Xanthium strumarium L.) to nicosulfuron was investigated both in field experiments and in the laboratory. Population CC1 had no history of treatment with any herbicide, while population CC2 was treated with ALS inhibitor herbicides for six consecutive years. In the field, plants were treated post-emergence with nicosulfuron (0, 10, 20, 40, 60 and <st1:metricconverter ProductID="80 g" w:st="on">80 g</st1:metricconverter> ai ha-1) at four true leaves. Visual injury estimation and vegetative parameters (plant height, fresh weight, leaf area) were recorded about month after herbicide application. The acetolactate synthase (ALS) enzyme activity in response to herbicide concentrations of 0, 0.01, 0.1, 1, 10, 100 μ M was determined in vitro . GR50 values for vegetative parameters and I50 values for ALS activity were slightly greater for the CC2 than for the CC1population, but the results confirmed that neither population was susceptible to nicosulfuron. Namely, based on results for fresh weight, the population CC1 was about 3.9 and 2.6-fold more susceptible to nicosulfuron than population CC2 in two consecutive years, but differences were not so prominent for other parameters (plant height, leaf area and ALS activity), ranging from 1.18 to 1.8-fold. The differences between population CC1 and CC2 could be attributed to inter-population variability in susceptibility to nicosulfuron or could be the consequence of repeated application of ALS herbicides to the CC2 population during the six previous years. Future investigations are necessary in order to clarify this dilemma.