The reaction of isoprene with OH radicals has been investigated by ab initio molecular orbital theory. We report the energetics of four different pathways, involving the direct addition of OH to four of the carbon atoms. Calculations have been performed using both density functional theory (BHandHLYP) and Møller–Plesset perturbation theory to the second-order (MP2). Two pre-reactive complexes have been identified, whose stabilization energy with respect to the separated reactants is about 12 kJ mol−1. Their structure is similar to the ones previously reported for OH–ethene and OH–propene adducts: the OH radical is placed over either one of the double bonds at a distance of about 2.1 Å, with the H atom pointing towards the C–C bond. The geometries of the transition states corresponding to OH addition at the four different positions have been optimized. The calculated apparent activation energies are negative for addition at the terminal carbon atoms and in excellent agreement with the experimental measurements. Direct addition at the internal carbon atoms involves much higher energy barriers, and these pathways are expected to be negligible at normal temperatures. Thus, the observed formation of 3-methylfuran must occur after radical addition to the terminal carbon atoms, following a pathway such as the one proposed by R. Atkinson, S. M. Aschmann, E. C. Tuazon, J. Arey and B. Zielinska, Int. J. Chem. Kinet., 1989, 21, 594 (). Calculated overall rate constants are obtained, in excellent agreement with experimental values. The two-parameter equation for the calculated overall rate coefficient was found to be (2.12±0.42)×10−11 exp[(384±55)/T] cm3 molecule−1 s−1, while the best fit for the four channels studied here correspond to the following expressions: k1=(2.25±0.51)×10−11 exp[(253±62)/T], k2=(9.60±1.18)×10−13 exp[(−2871±35)/T], k3=(1.81±0.22)×10−12 exp[(−1567±33)/T], and k4=(2.39±0.27)×10−12 exp[(676±33)/T] cm3 molecule−1 s−1.