Efforts are under way to develop a phenotypic analysis assay capable of identifying and differentiating chemicals with the potential to induce irritation and IgE-mediated and T-cell-mediated sensitization. These studies compare results obtained with the irritancy/phenotypic analysis assay to those obtained in the mouse ear-swelling test (MEST) and the local lymph node assay (LLNA). Female BALB/c mice (5 animals per group) were exposed topically to the human sensitizers 2,4-dinitrochlorobenzene (DNCB) and potassium dichromate (PDC) as well as the irritant methyl salicylate (MSC), following the protocol for each assay. DNCB was identified as a sensitizer in the LLNA and phenotypic analysis assay at concentrations as low 0.25%. In the MEST, DNCB was considered positive in concentrations as low as 0.01 and 0.05% at the 24- and 48-h measurements of the MEST, respectively. PDC tested positive as a sensitizer in the LLNA and the phenotypic analysis assay at concentrations as low as 0.25 and 0.1%, respectively. In the MEST, PDC was negative at the 24-h time point and tested positive only at the 48-h measurement at the highest concentration tested, 0.5%. Both DNCB and PDC induced an elevation in total serum IgE at the 0.5% concentrations. MSC was negative for sensitizing potential at all concentrations tested in all four assays. Phenotypic analysis of lymph node cells removed from animals dosed with the three chemicals gave results similar to the LLNA, but had the advantageof detecting chemicals with the capacity to induce an increase in the IgE+ cell population.