The synthesis of protein and nucleic acids was studied by isotope incorporation and dilution in the plasmodia ofPhysarum polycephalum during periods of growth and differentiation (spherule formation). The total protein content decreased during starvation, but protein synthesis still occurred, probably at the expense of proteins previously synthesized during growth. Studies on leucine incorporation showed that protein synthesized during growth had a greater turnover than did protein formed by starving cultures, when both types of cultures were transferred to starvation conditions. Protein synthesis after prolonged starvation was rapidly and markedly decreased following the inhibition of RNA synthesis, whereas no such direct dependence on RNA synthesis was observed in growing cultures or during early starvation.The kinetics of RNA synthesis and the types of RNA formed were also shown to differ in growth and starvation. RNA turnover was low in growing cultures but substantial in starving cultures that were returned to growth medium. Qualitative differences in pulse-labeled RNA extracted from growing or starving cultures were revealed by methylated-albumin-kieselguhr column chromatography and sucrose gradient centrifugation. In starving cultures proportionately more labeled RNA was found in the lighter, non-ribosomal region of the gradient, and RNA from this region hybridized with denatured DNA to a greater extent than did other RNA fractions.