Summary:In the present study we examined the effects of a tumor‐associated fetal antigen (TAFA‐II) on the activity of natural killer (NK) cells isolated from human cancer patients. TAFA‐II suppressed the NK cell response of some patients, and the level of suppression appeared to be independent of tumor type or stage of cancer therapy. No significant correlations were found between lymphocyte, neutrophil, monocyte, or eosinophil populations and TAFA‐induced suppression of NK cell activity. TAFA‐II effects were also not attributable to Ia+cells or to OKT3, OKT4, or OKT8 positive cells. This work confirmed results obtained in the rat model, in which suppression appeared to be directly mediated on the NK cell.