Recent work has shown that DNA sequences related to the mammalian ras proto-oncogenes are highly conserved in eucaryotic evolution. A monoclonal antibody (Y13-259) to mammalian p21ras specifically precipitated a 23,000-molecular-weight protein (p23) from lysates of Dictyostelium discoideum amoebae. Tryptic peptide analysis indicated that D. discoideum p23 was closely related in its primary structure to mammalian p21ras. p23 was apparently derived by post-translational modification of a 24,000-molecular-weight primary gene product. The amount of p23 was highest in growing amoebae, but declined markedly with the onset of differentiation such that by fruiting body formation there was less than 10% of the amoeboid level. The rate of p23 synthesis dropped rapidly during aggregation, rose transiently during pseudoplasmodial formation, and then declined during the terminal stages of differentiation. There was, therefore, a strong correlation between the expression of the ras-related protein p23 and cell proliferation of D. discoideum.