The protonation equilibria of cysteine and its complex formation with the Tl(I) ion were studied over a wide range of pH (1 to 11), using a combination of spectrophotometric and potentiometric methods at constant temperature, 25 degrees C, different methanol-water mixtures, (0 to 40) % (v/v), and constant ionic strength (0.1 mol.dm(-3) sodium perchlorate). Least-squares regression calculations are consistent with the formation of TlH(2)L(+), TlHL, and TlL(-) species, where L(2-) represents the fully dissociated ligand. The protonation of cysteine and the formation constants of the formed complexes in different media were analyzed in terms of Kamlet, Abboud, and Taft (KAT) parameters. Single-parameter correlations of the formation constants versus alpha (hydrogen-bond donor acidity), beta (hydrogen-bond acceptor basicity), and for pi* (dipolarity/polarizability) are relatively poor in all solutions, but multiparameter correlations represent significant improvements with regard to the single-parameter model. Linear correlation is observed when the experimental log beta(xyz) values are plotted versus the calculated ones, while all the KAT parameters are considered. Finally, the results are discussed in terms of the effect of solvent on protonation and complexation.