Cyclin D1 messenger RNA expression was investigated in differentiated proliferation-competent primary cultures of adult rat hepatocytes. Periodic expression was observed during the 12-day growth cycle (approximately two population doublings). Upon reaching a quiescent G(o)-state, 4-kb cyclin D1 mRNA levels were undetectable. When G(o) cultures were shifted into defined media without or with 0.2-0.8 nM TGF-alpha, conditions that reinitiate full proliferative transitions synchronously, cyclin D1 mRNA levels were elevated 1.2-4.6-fold, respectively. These findings support the hypothesis that hepatic mitogens stimulate periodic cyclin mRNA expression directly.