Ubiquitin-activating enzyme, "E1", is the first enzyme in the pathway leading to formation of ubiquitin-protein conjugates. We present immunocytochemical evidence that Ubiquitin-activating enzyme is concentrated in the cell nucleus. This finding points to the nucleus as the major site of action of this enzyme. Since ubiquitin itself is not similarly compartmentalized, this result suggests a high level of ubiquitin conjugate formation in the nucleus with a rapid turnover of ubiquitin conjugates.