Noncytotoxic aqueous extracts of esophageal tumors (TEx) inhibit the spontaneous uptake of 3H-thymidine by human peripheral blood mononuclear cells (PBM). TEx also inhibits mitogen- and antigen-induced PBM blastogenesis, mitogenesis, 3H-thymidine uptake, and 3H-leucine incorporation. Inhibition is reversible and is mediated by a heat-labile protein with a m.w. of approximately 70 to 80,000 daltons. Inhibitory activity is not due to trivial binding of mitogen or neucleotide by the inhibitor, nor is it entirely tumor specific since similar but quantitatively less activity is extractable from adjacent normal esophageal mucosa. Assorted cell surface membrane phenomena such as contact inhibition of in vitro endothelial cell proliferation, lymphocyte E rosette formation, and cap formation are unaffected by TEx. In contrast, immunoglobulin synthesis by pokeweed mitogen-stimulated PBM is enhanced by TEx. The potential importance of the local production of immunoregulatory agents like TEx in the immunologic control of tumor cell growth is discussed.