We have measured the kinetics of the helix-coil transition for the synthetic 21-residue peptide Ac-WAAAH(+) (AAAR(+)A)(3)A-NH2 initiated by nanosecond laser temperature jumps. This peptide was designed with tryptophan in position 1 and histidine in position 5 so that the side chains interact when the backbone of residues 1-5 is alpha-helical. Histidine, when protonated, efficiently quenches tryptophan fluorescence providing a probe for the presence of helical structure. The kinetics measured throughout the melting transition are well-described by a single-exponential relaxation, with a rate of 3.3 x 10(6) s(-1) at 301 K, the midpoint of the helix-coil transition. The rate increases with increasing temperature with an apparent activation energy of approximately 8 kcal/mol. To interpret these results we have fitted the equilibrium and kinetic data with the statistical mechanical model of Munoz et al. (Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 5872-5879). This model includes both variable helix propensities and side chain-side chain interactions. The model accounts for the single-exponential kinetics by predicting that approximately 90% of the change in the tryptophan fluorescence results from melting of stretches of helix which include residues 1-5 by passage over a nucleation free energy barrier. The measured temperature dependence is reproduced by introducing damping from solvent friction and an activation barrier for the individual helix propagation and melting steps. This barrier is somewhat larger than that which results from the loss in conformational entropy or breaking of hydrogen bonds. The model provides a description of the kinetics of the helix-coil transition which is consistent with the results of other experimental studies as well as molecular dynamics simulations.