The effect of various concentrations of nicotine and water soluble fraction from whole cigarette smoke on the transformation of rabbit peripheral lymphocytes by concanavalin A and goat anti-rabbit Fab was determined. The results demonstrated that incorporation of H3-thymidine into DNA by lymphocytes stimulated with optimal concentrations of these mitogens was inhibited in a dose-dependent manner by nicotine and water soluble fraction, and that this suppression was not a results of cytotoxicity. The response of lymphocytes to goat and rabbit Fab was slightly more sensitive to suppression by nicotine and water soluble fraction than was the response induced by concanavalin A. Moreover, water soluble fraction was more suppressive than nicotine. These results indicate that nicotine and water soluble fraction are not mitogenic.