TH 2.2 is a cloned (B lymphoma X B lymphocyte) somatic cell hybrid line which responds to exposure to bacterial polysaccharide by reduced growth, and by the secretion of the cytokines IL-3, IL-6, and GM-CSF, as well as by increased secretion per cell of IgM above the amount secreted constitutively. Exposure of TH 2.2 to amounts of LPS in doses >1fg/ ml, but not to lower doses renders the cells unresponsive to many of the inductive effects of LPS. The unresponsiveness lasts at least 20 cell generations, but is recovered eventually. Maintenance of unresponsiveness may depend on the presence of fetal calf serum in the growth medium; transfer of unresponsive cells to medium with very low concentrations of serum or to serum-free medium restores responses substantially or completely. Clonal analysis shows that several individual, highly sensitive clones can each be rendered unresponsive by treatment with LPS, and that individual unresponsive clones obtained from pretreated cells usually recover responsiveness. Finally, we have obtained promising results with an "ELISABLOT" assay for secreted products, beginning with IgM. This assay can enumerate secreting cells, and can be adapted to the measurement of the amounts secreted by each cell. These studies aim to understand the functional diversity found in many cell lines when clonal progeny or individual cells are examined. There is evidence that some of this diversification can be modified or regulated. The fact that LPS can nonpermanently modify the reponse to itself suggests that cell behavior can be modified by treatments relatively remote in time from the stimuli studied. Modulation of resistance to LPS by change of medium also suggests that "background" signalling may be important in determining responses to signals.