p-Cresol is a metabolite of aromatic amino acid metabolism produced by intestinal microflora, and its formation is influenced by intestinal conditions. Fasting drastically changes intestinal conditions. However, the effect of fasting on p-cresol production is unclear. In this study, serum and cecal p-cresol levels were determined in non-fasted rats and in rats fasting for either 12 or 18 h. Serum p-cresol increased significantly with 12-h fasting (3.44 +/- 2.15 nmol/ml; P<0.05) and 18-h fasting (5.40 +/- 2.20; P<0.001) as compared to the level in the non-fasted rats (1.02 +/- 0.50). Cecal p-cresol levels of the 12-h fasted (272.6 +/- 313.2 nmol/cecum) and 18-h fasted rats (436.6 +/- 190.8; P<0.01) were higher than those in non-fasted rats (27.1 +/- 21.9). The total cecal protein in content did not change with 18-h fasting. However, the cecal protein concentration increased significantly with fasting (P<0.001), and correlated closely with total cecal p-cresol contents (P<0.001). These results indicate that fasting enhances p-cresol production in the rat cecum, resulting in accumulation of serum p-cresol. We presume that the increase in p-cresol produced by fasting is related to the enhancement of bacterial nitrogen metabolism via an increased concentration of endogenous protein in the cecum.