The purpose of this study was to determine the concentration of leukotriene C4 (LTC4), a potent inflammatory mediator, in human symptomatic and asymptomatic periradicular lesions. Periradicular lesions from each of six asymptomatic and symptomatic patients were obtained. Six pulps from unerupted third molars served as the negative controls, six samples of chronically inflamed gingival tissues served as the positive controls. All samples were immediately frozen in liquid nitrogen. The concentration of LTC4 was determined by reverse-phase high-pressure liquid chromatography. Representative samples from each group were fixed in formalin, sectioned and stained with haemotoxylin and eosin. The concentrations of LTC4 found in the periradicular lesions were significantly higher than those in uninflamed pulpal tissue (P = 0.027). However, no statistically significant difference was found between the concentration of LTC4 in the periradicular lesions of the symptomatic patients and those found in the asymptomatic patients and in the samples of the chronically inflamed gingival tissue (P > 0.05). This data would suggest that among other inflammatory mediators, LTC4 participates in the pathogenesis of human periradicular lesions.