The active components of Aloe vera gel that can prevent ultraviolet B (UVB)-induced suppression of accessory cell function of Langerhans cells (LC) were purified by activity-guided sequential fractionation followed by in vitro functional assay. The functional assay was based on the fact that exposure of freshly isolated murine epidermal cells (EC) to UVB radiation resulted in impairment of accessory cell function of LC, as measured by their ability to support anti-CD3 monoclonal antibody (mAb)-primed T-cell mitogenesis. This UVB-suppressed LC accessory cell function was prevented by addition of partially purified Aloe gel components to cultures of UVB-irradiated EC. The Aloe gel components appeared to prevent events occurring within the first 24 h after UVB irradiation that lead to the impairment of accessory cell function. The Aloe gel components did not cause proliferation of anti-CD3 mAb-primed T-cells, nor did induce proliferation of normal EC. The activity-guided final purification of Aloe gel components resulted in the isolation of two components. Both of the components were small molecular weight (MW) substances with an apparent MW of less than 1,000 Da but different from each other in net charge characteristics at pH 7.4. These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.