The mechanism of resistance was investigated in a biotype of Setaria viridis resistant to aryloxyphenoxypropanoate and cyclohexanedione herbicides. Uptake of fenoxaprop-ethyl and diclofopmethyl was equal in the resistant and susceptible biotypes. In addition, metabolism of these two herbicides was similar in the resistant and susceptible biotypes, indicating that resistance is not based on altered herbicide metabolism. Fenoxaprop, diclofop, quizalofop, clethodim, sethoxydim, and tralkoxydim inhibited acetyl-coenzyme A carboxylase (ACCase) extracted from the susceptible biotype, with I50 values ranging from 0.078 to 1.7 ·M. ACCase from the resistant biotype was much less sensitive to all herbicides, with I50 values 31 to 60 times higher than for the susceptible biotype. These results indicate that herbicide resistance in this S. viridis biotype is conferred by an altered form of ACCase that is much less sensitive to a wide range of aryloxyphenoxypropanoate and cyclohexanedione herbicides. © 1993 by Academic Press, Inc.