Five biotypes of common cocklebur that were not controlled with acetolactate synthase (ALS)-inhibiting herbicides were tested in greenhouse and laboratory studies to determine the magnitude of resistance and cross-resistance to four ALS-inhibiting herbicides. In vivo inhibition of ALS was also evaluated. Based on phytotoxicity, all five ALS-resistant biotypes of common cocklebur were > 390 times more resistant than the susceptible biotype to imazethapyr. However, only four of these biotypes were also resistant to another imidazolinone, imazaquin. Two biotypes were cross-resistant to the sulfonylurea, chlorimuron, and the triazolopyrimidine sulfonanilide, NAF-75. One biotype demonstrated intermediate susceptibility to imazaquin, chlorimuron, and NAF-75. In all cases, the resistance exhibited at the whole plant level was associated with an insensitive ALS.