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This paper describes our efforts to study structure-activity relationships, improve the antimetastatic potency, and limit the in vivo enzymatic degradation of YIGSR-NH2, a synthetic peptide from the B1 chain of laminin, which reportedly has potential as an antimetastatic agent. To this end we have synthesized a series of psi (CH2NH) peptide analogs (5-9) of YIGSR-NH2 and a number of peptides in which the Tyr residue was replaced with D-Tyr (1), Phe (2), Phe (p-F) (3), and Phe(p-NH2) (4). All new peptides were assayed in vitro for their ability to promote cell attachment in both B16F10 mouse melanoma cells and HT-1080 human fibrosarcoma cells. On the basis of the in vitro assay results, peptides 3-5, 8, and 9 were tested in vivo for their ability to inhibit tumor metastasis to the lungs in mice that were coinjected in the tail vein with B16F10 melanoma cells and 1 mg of peptide. In summary, of the nine new peptides only the Phe(p-NH2) peptide 4 showed consistent in vitro cell attachment activity, but only low in vivo antimetastatic activity.