The acid dissociation constants (pK(a)) of eight biologically active pyridyl Shiff bases were determined using a UV-vis spectroscopic technique at 25 +/- 0.1 degrees C. The first acidity constants (pK(a1)) of the 2-[2-aza-2-(3-methyl-(2-pyridly))vinyl]phenol (1), 2-[2-aza-2-(3-methyl-(2-pyridly))vinyl]-6-nitrophenol (2), 2-[2-aza-2-(3-methyl-(2-pyridly))vinyl]-4-nitrophenol (3), 2-[2-aza-2-(3-methyl-(2-pyridly))vinyl]-4,6-dinitrophenol (4), 2-[2-aza-2-(5-methyl-(2-pyridly))vinyl] phenol (5), 2-[2-aza-2-(5-methyl-(2-pyridly))vinyl]-6-nitrophenol (6), 2-[2-aza-2-(5-methyl(2-pyridly))vinyl]-4-nitrophenol (7), and 2-[2-aza-2-(5-methyl-(2-pyridly))vinyl]-4,6-dinitropheno1 (8) are found to be associated with the protonation of phenolate oxygen. The second acidity constants (pK(a2)) are found to correspond to protonation of pyridine nitrogen for compounds 5, 6, and 7 and oxoprotonation for molecules 1, 2, 3, 4, and 8. The third acidity constants (pK(a3)) are found to be associated with the protonation of pyridine nitrogen for compounds 1, 3, 7, and 8 and amino protonation for molecules 2 and 5. For molecules 4 and 6, it is associated with oxo protonation. The contribution of the ketoamino tautomeric form was found to be considerably important.