Cutaneous exposure to ultraviolet radiation suppresses the induction of T cell mediated responses such as contact and delayed type hypersensitivity (DTH) by altering the function of immune cells in the skin and causing the release of immunoregulatory cytokines. Extracts of crude Aloe barbadensis gel prevent this photosuppression. Because the regulation of contact hypersensitivity and DTH responses differ, we investigated whether protection was afforded by a single or multiple agents in Aloe and the mechanism by which this material prevents suppression of DTH immunity. The ability of Aloe gel to prevent suppression of contact hypersensitivity responses to hapten decayed rapidly after manufacture. In contrast, agents that protected against systemic suppression of DTH responses to Candida albicans were stable over time. Oligosaccharides prepared from purified Aloe polysaccharide prevented suppression of DTH responses in vivo and reduced the amount of IL-10 observed in ultraviolet irradiated murine epidermis. To assess the effect of Aloe extracts on keratinocytes, Pam 212 cells were exposed in vitro to ultraviolet radiation and treated for 1 h with Aloe oligosaccharides. Culture supernatants were collected 24 h later and injected into mice. Supernatants from ultraviolet irradiated keratinocytes suppressed the induction of DTH responses, whereas Aloe oligosaccharide treatment reduced IL-10 and blocked the suppressive activity of the supernatants. These results indicate that Aloe contains multiple immunoprotective factors and that Aloe oligosaccharides may prevent ultraviolet induced suppression of DTH by reducing keratinocyte derived immunosuppressive cytokines.