We have previously shown that a factor(s) in rat serum induces ornithine decarboxylase (ODC) in incubated muscle and that its activity is diminished in sera from diabetic rats. To characterize this factor further, we have studied some of its physicochemical and biologic properties. As judged from its ability to induce ODC in the incubated rat soleus muscle, the factor is protease-sensitive and both heat- and acid-stable. In untreated whole serum its activity is associated with a high-molecular-weight fraction whereas after boiling at pH 5.5, activity is principally in a fraction with a molecular weight between 3500 and 12,000 daltons. The activity of the factor is diminished in hypophysectomized, starved, and aged as well as diabetic rats. In diabetic rat serum it is restored to normal by the addition of a purified somatomedin, multiplication-stimulating activity. These findings suggest that the "ODC inducing factor" is a low-molecular-weight peptide and that it has many of the characteristics of a somatomedin.