A wide spectrum of formalin-killed bacteria have been tested for their ability to release histamine from human dispersed lung and tonsillar mast cells. Escherichia coli, Enterobacter cloacae, Staphylococcus epidermidis, Proteus vulgaris, Klebsiella oxytoca and K. pneumoniae were the most effective histamine releasers. Further studies on tonsillar masl cells showed that E. coli-induced histamine release differed from IgE-dependent release with respect to its kinetics, temperature and pH profiles and its sensitivity to calcium deprivation and metabolic inhibitors. A lectin-mediated mechanism may operate, but other non-immunological mechanisms might also be involved in the release. Escherichia coli and anti-IgE did not synergize in inducing histamine release. The production of PGD2 and the failure to detect lactate dehydrogenase following incubation of mast cells with E. coli suggests that histamine release is not due to cytotoxicity.