The effect of acetylsalicylic acid (aspirin) on peptic degradation of gastric mucin, its viscosity and the ability to retard the diffusion of hydrogen ion was investigated. The results of peptic degradation indicated that, in the absence of the drug, the rate of proteolysis was proportional to mucin concentration up to 400 micrograms and remained constant with time for up to 1 hr. Introduction of aspirin led to an enhancement in the rate of proteolysis. The apparent Km value of pepsin toward mucus glycoprotein was 8.7 X 10(-7) M in the absence of the drug and 6.9 X 10(-7) M in its presence. Viscosity measurements showed a drop in mucin viscosity following preincubation with aspirin. This decrease was concentration dependent and at a 4.0 X 10(-5) M concentration of the drug reached a value of 75%. Permeability studies revealed that preincubation with 2.0 X 10(-5) M aspirin increased the permeability of mucin to hydrogen ion by 10%, while an 18% increase was obtained with 4.0 X 10(-5) M aspirin. The results suggest that aspirin weakens the integrity of the gastric mucus layer by promoting its peptic degradation, decreasing viscosity, and reducing the ability to resist hydrogen ion penetration.