The ability of human IgE-anti-IgE (mouse hybridoma anti-Fc) immune complexes (IC) to generate suppressor T cells for human myeloma IgE synthesis in vitro was tested. T cells incubated with 0.1 micrograms/ml of IC that had an IgE to anti-IgE ratio of 1:1 inhibited myeloma IgE synthesis by 16% more than the control (p less than 0.01). Inhibition was also seen with IC in which the IgE to anti-IgE ratio was higher (2:1 and 4:1), but these differences in synthesis were smaller and were not statistically significant (8 and 3%, respectively, p greater than 0.05). Thymidine incorporation by T cells incubated 3 days with 0.1 microgram/ml of IC at the 1:1 or 2:1 ratio was consistently greater (p less than 0.0025 and less than 0.0125, respectively) than by controls. The IC lost their ability to generate suppressor T cells when the cytophilic site on the IgE molecule was destroyed with heat treatment (0% inhibition with IC at 1:1 and 4% inhibition with IC at 2:1). The activation of T cells with IC showed isotype specificity because the activated T cells failed to suppress IgG and IgA synthesis by the lymphoblastoid cell lines GM-1500 and GM-1056, respectively. T cells were fractionated by incubation with IC and then were panned on plates coated with goat anti-mouse IgG. The adherent cells spontaneously suppressed IgE by 25% when compared to controls (p less than 0.005). These cells failed to suppress IgG and IgA. The activation of the T cells was not due to the panning process itself because activation did not occur with cells that adhered to plates coated with bovine serum albumin (p greater than 0.05) when compared to untreated T cell controls or the IC nonadherent population. These experiments extend previous findings that isotype-specific suppressor T cells for IgE synthesis can be generated in vitro.