A waterhemp population (McLean County resistant, MCR) from McLean County,Illinois is resistant to both mesotrione and atrazine by elevated rates ofherbicide metabolism. Research was conducted to investigate the inheritanceof these resistance traits. Resistant and sensitive plants were crossed toobtain reciprocal F1 populations, which were then used to create pseudo-F2 and backcross (to sensitive parent; BCS)populations. The various populations were evaluated with whole-plantherbicide efficacy studies in a greenhouse. The responses of the F1 populations to both mesotrione and atrazine wereintermediate when compared with parental populations. In the case ofatrazine, BCS and F2 populations segregated 1 : 1 and1 : 3, respectively, for susceptibility (S) : resistance (R), at a dose thatcontrolled the sensitive parent but not the F1 or resistantparent. For mesotrione, variability was observed within the F1populations, suggesting that mesotrione resistance is multigenic and theresistant parents used in the cross were not homozygous at the resistanceloci. Furthermore, at low mesotrione doses, more F2 plantssurvived than expected on the basis of a single-gene trait, whereas at highdoses, fewer F2 plants survived than expected. Dry weight dataconfirmed the conclusions obtained from survival data. Specifically,atrazine responses segregated into two discrete classes (R and S) in boththe F2 and BCS populations, whereas mesotrioneresponses showed continuous distributions of phenotypes in F2 and BCS populations. We conclude that metabolism-based atrazineresistance in MCR is conferred by a single major gene, whereas inheritanceof mesotrione resistance in this population is complex.