Spices have long been implicated as a cause of gastric mucosal injury. We assessed the effects of red and black pepper on the gastric mucosa using double-blind intragastric administration of test meals containing red pepper (0.1-1.5 g) or black pepper (1.5 g) to healthy human volunteers; aspirin (655 mg) and distilled water were used as positive and negative controls, respectively. Serial gastric washes were performed after test meal administration and gastric contents were analyzed for DNA, pepsin, blood, sodium, potassium, parietal cell secretion, and nonparietal cell secretion. Both red pepper and black pepper caused significant increases in parietal secretion, pepsin secretion, and potassium loss. Gastric cell exfoliation (as reflected in DNA loss into gastric contents) was increased after red or black pepper administration; the increase after red pepper administration was dose dependent. Mucosal microbleeding was seen after spice administration and one subject had grossly visible gastric bleeding after both red pepper and black pepper administration. There were no significant differences from control between the test meals, in nonparietal volume, fractional recovery of the gastric secretions, or sodium secretion. Finally, no spice was significantly different from aspirin in any parameter studied; indeed, aspirin was comparable to the higher doses of pepper. The long-term result of daily pepper ingestion is unknown. Whether spices are detrimental, beneficial (e.g., inducing an adaptive cytoprotective response), or have no significant long-term effect on the gastric mucosa is unknown and deserves further study.