AbstractThis study was undertaken to determine whether and by what means particles which induce granulomatain vivocan affect murine spleen lymphoproliferative and antibody responsesin vitro. Particles of silica, talc, Bentonite orC. parvumcells inhibited lipopolysaccharide‐ or concanavalin A‐stimulated proliferation and sheep red blood cell‐induced antibody responsein vitro. The inhibition required at least 48 hours exposure of the cells to the particles. The late onset of inhibition and its reproducibility at different cell or mitogen concentrations implicated particle‐induced injury to both phagocytes and lymphocytes. Either α‐tocopherol or 2‐mercaptoethanol prevented the particle‐induced inhibition of spleen cell responses. α‐Tocopherol and 2‐mercaptoethanol have in common the capacity to protect cells against membrane lipid peroxidation. The inhibitory peroxidative process(es) implicated by these studies are most likely attributable to: (a) stimulation of oxidative metabolism of phagocytic cells by particles; and (b) iron‐catalyzed peroxidation directly by the particles. These data may be relevant in understanding the pathogenesis of and devising therapeutic approaches toward various gra