The purpose of this study was to quantify the degree of suppression of the perceived bitterness of quinine by various substances and to examine the mechanism of bitterness suppression. The following compounds were tested for their ability to suppress bitterness: sucrose, a natural sweetener; aspartame, a noncaloric sweetener; sodium chloride (NaCl) as the electrolyte; phosphatidic acid, a commercial bitterness suppression agent; and tannic acid, a component of green tea. These substances were examined in a gustatory sensation test in human volunteers, a binding study, and using an artificial taste sensor. Sucrose, aspartame, and NaCl were effective in suppressing bitterness, although at comparatively high concentrations. An almost 80% inhibition of bitterness (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Similar levels of bitterness inhibition by phosphatidic acid and tannic acid (81.7, 61.0%, respectively) were obtained at much lower concentrations (1.0 (w/v)% for phosphatidic acid and 0.05 (w/v)% for tannic acid). The mechanism of the bitterness-depressing effect of phosphatidic acid and tannic acid was investigated in terms of adsorption and masking at the receptor site. With phosphatidic acid, 36.1% of the bitterness-depressing effect was found to be due to adsorption, while 45.6% was due to suppression at the receptor site. In the case of 0.05 (w/v)% tannic acid, the total bitterness-masking effect was 61.0%. The contribution of the adsorption effect was about 27.5% while the residual masking effect at the receptor site was almost 33%. Further addition of tannic acid (0.15 (w/v)%), however, increased the bitterness score of quinine, which probably represents an effect of the astringency of tannic acid itself. Finally, an artificial taste sensor was used to evaluate or predict the bitterness-depressing effect. The sensor output profile was shown to reflect the depressant effect at the receptor site rather well. Therefore, the taste sensor is potentially useful for predicting the effectiveness of bitterness-depressant substances.