The introduction of activated c‐myc and v‐myc genes into a variety of non‐established and established cells results in the suppression of endogenous c‐myc expression. As measured in Rat‐1 fibroblasts, the suppression occurs at the level of transcriptional initiation. Moreover, the extent of the down‐regulation is proportional to the cellular concentration of c‐myc protein, and the critical concentration range in which the endogenous c‐myc RNA is effectively suppressed corresponds to that found in non‐transformed cells. In addition, the autoregulatory mechanism is not only dependent on c‐myc protein, but also requires additional trans‐acting factors. These results support a role for c‐myc in the regulation of cellular gene transcription and suggest that a negative feedback mechanism can act as a homeostatic regulator of c‐myc expression in vivo.