We have isolated two cationic macromolecules from normal human serum that induce contact-inhibited cells to synthesize DNA and divide; these factors are not necessary for the growth of viral-transformants. They have been obtained from pooled normal human sera by ion exchange chromatography (Dowex-50w-x8, Na ion cycle) and have been further purified by gel filtration and preparative isoelectric focusing on polyacrylamide gel. The latter technique produced two components, one with an isoelectric point between pH 9.7 and 9.9 which was free of insulin-like activity, and the other with an isoelectric point between 8.6 and 9.0 associated with insulin-like activity. These factors have been purified 1,500-7,000 fold. We propose to isolate these macromolecules, elucidate their chemical structure, and study their mechanism of action. Furthermore, a radioimmunoassay will be developed to study their presence in human sera in both health and disease.