Populations of Setaria faberi and Digitaria sanguinalis cross-resistant to sethoxydim and fluazifop-P-butyl were identified in a vegetable cropping system in Wisconsin, USA, in 1991 and 1992 respectively. Experiments were conducted with partially purified acetyl-CoA carboxylase (ACCase) to determine whether resistance to sethoxydim and other ACCase inhibitors in S. faberi and D. sanguinalis resulted from altered enzyme activity. Based on I 50 values (the herbicide dose that inhibited ACCase activity by 50% compared with untreated ACCase), ACCase of the resistant accession of S. faberi was 4.8-, 10.6-and 319-fold resistant to clethodim, fluazifop-P acid and sethoxydim, respectively, compared with that of the susceptible accession. Similarly, ACCase of the resistant accession of D. sanguinalis was 5.8-, 10.3and 66-fold resistant to clethodim, fluazifop-P acid and sethoxydim respectively. These results indicated that resistance to ACCase inhibitors in these accessions of S. faberi and D. sanguinalis resulted from an altered ACCase enzyme that confers a very high level of resistance to sethoxydim.