The observations that p19Arf and p53 were upregulated in papillomas, that p53 expression was reduced in p19 Arf-null papillomas, and that loss of p19Arf had a similar effect on tumor progression as that of loss of p53, provide strong in vivo support of the model whereby p19Arf regulates p53 in response to mutational activation of Hras. However, enhanced tumor growth in p19 Arf-null mice, in contrast to reduced tumor growth in p53-null mice (Kemp et al. 1993), suggests additional tumor suppressor functions of p19Arf, independent of p53. This evidence concerns the gene TP53 and papilloma.