Bacterial lipopolysaccharide (LPS), being a B cell mitogen, enhances antibody production. When given prior to an injection of sheep red blood cells (SRBC) it caused a premature but not significantly increased production of antibody forming cells in regionally stimulated lymph nodes. There was a corresponding depression of T cell activity, as measured by the relative levels of delayed-type hypersensitivity (DTH) in normal and LPS-treated mice. Although LPS also induced hyperplasia of the reticuloendothelial system, and a consequent reduction in the effective antigenic dose of SRBC, this was not the reason for the reduced level of T cell activity. The opposing effects of LPS on T and B cell responses was due to premature inhibition of the T cell response by an accelerated production of antibody. This caused an earlier onset of the inhibitory mechanism which regulates the T cell response and is specific for the inducing antigen.