Staphylococcus enterotoxins and toxic shock syndrome toxin-1 (TSST-1) are members of the family of staphylococcal exoproteins (SE) which binds specifically to HLA class II molecules and certain V beta T cell receptor phenotypes. These bacterial products have been termed "superantigens" due to their capacity to stimulate a greater proportion of T lymphocytes than peptide antigens without a requirement for antigen processing. The SE stimulate monocytes to secrete IL-1 and TNF-alpha and affect B lymphocyte proliferation in response to anti-human IgM and Ig production by PBMC. The current study concerns the transmission of signals in human B lymphocytes following fixation of TSST-1. Activation of both PLC and PKC are observed while intracellular calcium levels remain unchanged. Levels of HLA class II mRNA were increased suggesting that a pathway leading to activation was triggered. This study therefore identifies some of the second messengers involved after SE fixation on HLA class II molecules and suggests that the signals transmitted via class II antigens as well as those via the TCR may have a role in the physiological responses to bacterial superantigens.