The reaction of isoprene with nitrate radicals (NO3) has been investigated using combined experimental and theoretical approaches. A fast-flow reactor coupled to chemical ionization mass spectrometry (CIMS) detection was used to measure the rate constant of the NO3-isoprene reaction, yielding a value of (7.3 +/- 0.2) x 10(-13) cm(3) molecule(-1) s(-1) in the pressure range of 5-7 Torr and at 298 +/- 2 K. The reaction product, the NO3-isoprene adduct radical, was directly detected using the CIMS method. In addition, density functional theory and ab initio molecular orbital calculations have been employed to determine the structures and energies of the NO3-isoprene adduct isomers. Geometry optimizations were performed using density functional theory at the B3LYP/6-31G(d,p) level, and the single-point energies were computed using second-order Moller-Plesset perturbation theory and the coupled-cluster theory with single and double excitations including perturbative corrections for the triple excitations (CCSD(T)). At the CCSD(T)/6-31G(d) level of theory, the zero-point-corrected energies of the NO3-isoprene adduct radicals are 15 to 31 kcal mol(-1) more stable than the separated NO3 and isoprene, and the isomers of terminal NO; additions are more energetically favorable than those of internal NO3 additions. The rate constants of the formation of the NO3-isoprene adduct radicals and their isomeric branching have been calculated using the canonical variational transition state theory.