Spinach leaves treated with acifluorfen synthesize >25-fold the normal level of the phenolic amide (I) derived from ferulic acid and 3-methoxytyramine. The content of I is increased within 18 hr and at acifluorfen concentrations as low as 0.2 ppm. Biosynthesis experiments with precursor 14C-amino acids establish that the elevated content of I is due to de novo synthesis with the acyl moiety derived from phenylalanine, the amine moiety from tyrosine, and the O-methyl groups from methionine. Elevation of I content is followed by the appearance of necrotic lesions in spinach leaves but is preceded by an increase in extractable phenylalanine ammonia-lyase activity, detectable 9 hr after treatment, reaching 13-fold of normal values at 20 hr, and dropping to near control activity at 48 hr. Phenylalanine ammonia-lyase activity is also elevated by acifluorfen in soybeans and six other crops or weeds. Alterations in aromatic amino acid metabolism and phenylpropanoid biosynthesis involving secondary phenolic compounds may contribute to the phytotoxic effects of diphenyl ether herbicides.