Ethanol reportedly is immunosuppressive, interfering with lymphocyte proliferation. To investigate the basis for this immunosuppression, the effects of acute treatment with ethanol were studied on Ca2+ mobilization in tonsillar B lymphocytes and the human lymphoblastoid B‐cell line, Ramos. The level of intracellular Ca2+ was monitored in cells loaded with the fluorescent dye indo‐1 following stimulation with either anti‐lgM antibody or platelet activating factor. The effect of ethanol was also examined on the induction of the early proto‐oncogene c‐fos in these cells. Ethanol inhibited ligand‐activated Ca2+ mobilization due to transmembrane influx but not intracellular store release, in a dose‐and time‐dependent manner. This inhibition was not due to the inability of anti‐lgM to bind to its surface receptor nor to membrane depolarization induced by ethanol. Ethanol also inhibited the Ca2+‐dependent induction by anti‐lgM of c‐fos in these cells. The inhibitory effects of ethanol on ligand‐activated Ca2+ channels and subsequent induction of c‐fos may provide the basis for its immunosuppressive action. © 1992 Wiley‐Liss, Inc.