To develop a small peptide antagonist for a cytokine, an oligopeptide ligand interacting with interleukin-6 (IL-6) has been screened by affinity panning from a random heptapeptide displaying phage library. After biopanning five times against IL-6, ten phages displaying heptapeptides with consensus sequence, K(L/V)WXIPQ, were selected out of nucleotide sequencing of 21 phages. A synthetic oligopeptide, KLWTIPQ (P-1), was prepared but it did not inhibit growth of MH60, an IL-6 dependent cell line. To stabilize the structure of oligopeptide and bring stronger molecular hindrance In interaction between IL-6 and its two receptors (IL-6R and gp130), a peptide with two cysteine residues at each end of consensus sequence, GGCKLWTIPQCGG (PC), was also synthesized, which significantly inhibited cell growth of MH60 at over 100 mu M and phosphorylation of Stat3, which is primary signal transducer and activator of transcription, phosphorylated by IL-6 signal. These results strongly suggest that PC is specifically bound to IL-6 and hinders formation of IL-6/IL-6R/gp130 complex.