Transcription from the c-fos promoter and from minimal promoter constructs carrying the phorbol ester-responsive element [12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element (TRE)] corresponding to the sequence in the human collagenase gene is activated by elevated levels of the oncogene products v-src, c-Ha-ras, activated c-Ha-ras, and v-mos, as well as by phorbol ester. Elevated c- or v-fos expression stimulates TRE-dependent transcription but represses the c-fos promoter. Antisense fos sequences abolish basal and induced transcription from TRE constructs and derepress the c-fos promoter. These results establish a key role for fos in signal transduction and implicate the fos protein as a trans-activating and -repressing molecule.