Ultraviolet (UV) radiation induced inflammation plays an important role in the aging of human skin. Prostaglandin (PG) E(2) is the primary mediator of UVB induced photoinflammation. We screened an internal library for dipeptides that inhibited UVB induced PGE(2) synthesis but showed no cytotoxicity toward human keratinocytes. We identified three highly active inhibitory sequences, LE (Leu+Glu), MW (Met+Trp) and MY (Met+Tyr). To evaluate their efficacy in human skin, 24 sites of abdomen skin were irradiated with a 308 nm excimer laser (300 mJ/cm(2)), after which 2% LE, MW, MY or a control were applied to the irradiated sites for 24h. The erythema index (EI) was measured before and 24h after treatment. The results showed that LE and MW significantly decreased UVB induced erythema (p=0.041 and p=0.036, respectively), but ME did not. Overall, LE and MW are candidate cosmeceutical peptides that can protect skin from UVB induced photoinflammation.