Pharmacologically active mediators of inflammation were obtained from suction bullae raised on normal and ultraviolet B (290-320 nm) inflamed human abdominal skin. The exudates obtained from the bullae were examined by superfusion cascade bioassay, by radioimmunoassay for PGF2alpha and by column, thin-layer and gas-liquid chromatography. Ultraviolet B (u.v.-B) irradiation of human skin produced an erythema which appeared after 2 hr, increased in severity up to 24 hr and persisted for more than 48 hr. Bioassayable and radioimmunoassayable prostaglandin activity was elevated at 6 hr, was maximal at 24 hr and had returned to normal 48 hr. Topical application of indomethacin suppressed both the erythema and the increased concentration of PGF2alpha as measured by radioimmunoassay. Chromatographic studies confirmed increased prostaglandin activity at 6 and 24 hr and in addition demonstrated an increase in arachidonic acid-like activity. The results suggest that prostaglandins may play an important role between 6 and 24 hr of u.v.-B-induced erythema. Whether the reduction of erythema by indomethacin can be partially or wholly attributable to inhibition of prostaglandin biosynthesis is uncertain.