ZBP-89 is a Krüppel-type zinc finger transcription factor that binds to GC-rich sequences. Overexpression of this factor prevents EGF induction of the gastrin promoter; therefore, we postulated that ZBP-89 may modulate cellular proliferation. To test this hypothesis, ZBP-89 was overexpressed in immortalized (GH4) and malignant (AGS) cell lines. Growth parameters, e.g., 3H-thymidine, BrdU labeling, flow cytometry and ornithine decarboxylase promoter activity were analyzed. The results show that DNA synthesis is inhibited and progression to S phase is blocked in GH4 cells. Collectively, these studies demonstrate that ZBP-89 inhibits cellular proliferation at least in part through its ability to bind and repress ornithine deacarboxlyase promoter activity.