The expression of cytoskeletal protein genes may be linked to both cell growth and the status of the cytoskeleton. Actin gene expression was examined in murine erythroleukemia cells treated with the microfilament disrupting agent, cytochalasin D (CD), at a concentration which was determined to inhibit cell growth and arrest cells in the S and G1 phase of the cell cycle. Levels of actin mRNA and protein synthesis were elevated eight- and sixfold, respectively, after 9 h in CD. This increase was reflected in levels of nuclear run-on actin transcripts and prevented by actinomycin D, suggesting that enhanced transcription of the actin gene was responsible for the increase. Removal of CD resulted in immediate resumption of cell cycle progression with the accumulation of a G2-phase-enriched population and a rapid return of actin mRNA and protein synthesis to control levels (half-life 4.8 h). These results are consistent with a model linking actin gene expression to cell growth by regulating transcription during the G1 and mRNA decay during the G2 phase of the cell cycle.