The rapid, synchronous differentiation of N. gruberi from amoebae to flagellates is a useful paradigm to study aspects of cell differentiation, including regulation of the synthesis of proteins that are related to the changes in cell shape and motility, which occur during differentiation. The differentiation requires synthesis of new RNA and protein molecules to accomplish defined morphogenetic events. Specific new proteins, including the tubulins that form the flagellar microtubules, are synthesized at various times during differentiation, and particular mRNA species appear and disappear. The time course of the synthesis of the alpha and beta subunits of flagellar tubulin is paralleled by the programmed appearance and disappearance of flagellar tubulin mRNAs. The evidence supports the hypothesis that the synthesis of flagellar tubulin is regulated by the transcription, and subsequent disappearance, of flagellar tubulin mRNA. Translatable mRNAs for two calmodulin-like calcium-binding proteins appear and disappear contemporaneously with those for flagellar tubulin. During differentiation the synthesis of actin, the major protein of amoebae, is selectively shut down, and translatable actin mRNA rapidly disappears. This description of the orderly appearance, utilization, and disappearance of the mRNAs for actin, calcium-binding proteins, and flagellar tubulin during differentiation provides means and motivation to investigate the mechanisms that regulate these events.