The YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide, derived from the laminin β1 chain, decreases tumor metastasis and growth in experimental animals. The mechanism responsible for this inhibition is not known. We now report that a 16-mer branched form of YIGSR, synthesized by the multimeric antigen peptide system, induced the apoptosis of HT-1080 cells in vitro at 30 µg/ml (approximately 3 µm). Tumor cells treated with this peptide showed the expected morphological changes associated with apoptosis, acridine orange staining of nuclei, increased numbers of 3′-OH ends of DNA in nuclei, a DNA ladder pattern on agarose gels, and increased transforming growth factor β1 mRNA by Northern blot. The specificity of this peptide was confirmed by inhibition of apoptosis with a neutralizing antibody to the peptide. In addition, the branched 16-mer peptides of scrambled sequence did not induce apoptosis. Our in vitro results suggest that apoptosis may play a role in the antimetastatic and antitumor effects associated with the YIGSR peptide.