Cells induced to accumulate the p53 tumor suppressor protein have been shown to arrest in G1. This arrest is characterized by accumulation of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and of under-phosphorylated forms of retinoblastoma protein. We show here that accumulation of the wild-type p53 protein in either human or murine cells markedly increases expression of cyclin D1. The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. The relationship between the induction of cyclin D1 and G1 arrest defines a new cellular response to p53.