Four hours after an i.p. injection of 500 mg/kg nicotinamide, there was a decrease in kidney ODC activity, followed by a substantial increase by 24 h. Exposing rats to 0, 0.67, 6.7 and 30 mM nicotinamide in their drinking water for 7 and 28 days also resulted in a statistically significant increase in kidney ODC activity, but the rates of DNA synthesis were unaffected, as measured by incorporation of [3H]thymidine into DNA and % labeled proximal tubule nuclei; the total amount of DNA/kidney was also unaffected. The results of this investigation demonstrate that nicotinamide, a known renal tumor promoter, was able to induce a significant increase in ODC activity in the rat kidney without a concomitant increase in DNA synthesis, suggesting that early stimulation of ODC is associated with tumor promotion even in the absence of effects on DNA replication.