We have prepared125I-labeled cholera toxin B subunit (125I-labeled CT-B, a specific activity of 98 Ci/mmol) and found that its binding to T and B lymphocytes from the blood of healthy donors was high-affinity (Kd2.8 and 3.0 nM, respectively). The binding of labeled protein was completely inhibited by unlabeled thymosin-α1(TM-α1), interferon-α2(IFN-α2), and the synthetic peptide LKEKK that corresponds to residues 16–20 in TM-α1and 131–135 in IFN-α2, but was not inhibited by the synthetic peptide KKEKL with inverted amino acid sequence (Ki 10 μM). Thus, TM-α1, IFN-α2, and the peptide: LKEKK bind with high affinity and specificity to CT-B receptor on donor blood T and B lymphocytes. It was found that CT-B and the peptide: LKEKK at concentrations of 10–1000 nM increased in a dose-dependent manner the soluble guanylate cyclase activity in T and B lymphocytes.