Lymphocyte division has been the subject of many studies from the point of view of cellular immunology and antibody synthesis. Blast cell transformation and mitosis occur both in vitro and in vivo under stimulus from a number of agents which act on the cell surface, particularly in experimental situations by lectins (1).Although the sequence of events which connect the mitogenic stimulus to DNA synthesis is still incompletely known and several different cell types may be involved, a nmnber of preliminary changes have been recognized. Thus, for example, the cyclic AMP level in lymphocyte cultures rises within 2 rain of stimulation (2), membrane biosynthesis increases within 1/4 h of stimulation (3), nuclear template activity increases within 2 h (4). I t is of considerable importance to an understanding of the neoplastic change in lymphoid cells to know the extent to which such processes and factors controlling them are retained in replicating lymphoma cells, and the extent to which they are altered.We here report a comparison, between the effects of certain thiols and disulfides which we have found to be necessary for the growth of mouse lymphoma cells in vitro, and their effects in enhancing the action of mitogens on splenic lymphocytes.Our observations stem from the finding that mouse lymphoma cells of the line L1210 (V) which had previously been established in culture only with great difficulty (5), proliferate in a medium formulated by Balk (6). The specific growth promoting component of this medium was found to be its high concentration of added L-cysteine (1.5 mM) (7). As will be described, a number of thiols and disulfides can substitute for L-cysteine, some at very low concentration (to < 1 #M). Precise structure activity relationships exist. Furthermore, 13 of 23 other mouse leukemic and neoplastic lymphoid cell lines were also thiol-disulfide dependent in vitro.