The tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and the teleocidins (TCDs) had similar inhibitory effects on IgE binding onto the membrane of rat basophilic leukemia (RBL)-2H3 cells. The level of expression of the functional IgE Fc receptor (Fc epsilon R), as measured by CELISA, was decreased up to a maximum of 60% within 5 min-1 h of treatment. This inhibition was obtained at concentrations of 0.1 microgram/ml for most TCDs, of 1 microgram/ml for TPA and of 20 micrograms/ml for one TCD (olivoretin A). These molecules also decreased the amount of cell-bound IgE detectable by CELISA on cells that had been coated with IgE prior to TCD treatment. When incubated with RBL-2H3 cells for 30 min-2 h, the TCDs and TPA stimulated serotonin release. Depending on their concentration, they had various effects on IgE-plus antigen-induced serotonin release. It is suggested that the down-regulation of IgE receptor expression by these tumor promoters is mediated through protein kinase C activation and phosphorylation of the Fc epsilon R.