Hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) are the volatile sulfur compounds (VSC) that were investigated for a possible role in the etiology of periodontal disease. The results show that the permeability of porcine non-keratinized sublingual mucosa is increased by up to 75% or 103% following exposure to H2S and CH3SH, respectively. The effect may be attributed to VSC reaction with tissue components resulting in alteration in the integrity of the tissue barrier. The increase in permeability of the mucosa to [35S]-Na2SO4 was dependent on both the time of exposure and concentration of VSC in the head-space. The [35S]-H2S was retained by the mucosal tissue and was able to penetrate the intact layers consisting of non-keratinized epithelium, basal membrane, and connective tissue. Treatment of the mucosa with 0.22% ZnCl2, either prior to or after exposure to CH3SH, nullified the effect of CH3SH and restored the permeability to a state similar to that observed in control 95% air/5% CO2 systems.