Fibronectin is a major cell surface and extracellular matrix glycoprotein involved in cell adhesion and migration. A synthetic peptide containing the key fibronectin adhesive recognition sequence Gly-Arg-Gly-Asp-Ser administered intravenously substantially enhanced survival of mice challenged concurrently with melanoma cells in an experimental metastasis assay. Since renal clearance of the peptide was found to be very rapid, conjugation of a peptide derivative to a carrier is being tested as a means of increasing its time in the circulation. In addition to this original peptide recognition sequence, fibronectin was shown to contain a second binding site that synergizes with it to produce full adhesive affinity and efficient transmembrane effects of the peptide on cytoskeletal organization. Mutants produced by site-directed mutagenesis or deletion of each site displayed greater than 96 percent losses of activity, and the two types of mutants synergized in vitro for adhesion and promoting organization of actin microfilament bundles. Studies of this region may yield a novel class of inhibitor of fibronectin function. Two other cell adhesion sequences are present in only certain fibronectin molecules due to alternative mRNA splicing of another domain. Besides melanoma cells, embryonic cells from the peripheral nervous system were found to use this cell-type specific domain, which may be recognized only by cells derived originally from the neural crest. The Gly-Arg-Gly-Asp-Ser peptide and related analogues inhibited adhesion of embryonic cells involved in somite and heart formation. However, this peptide had unusual effects on segmental plate cells, which are the precursors of somites. The peptide substantially induced cell-to-cell aggregation, suggesting that it may regulate expression of a cell-cell adhesion system.