A primary kinetic isotope effect may be found when a bond to the isotopically labeled atom is being formed or broken. Depending on the way a kinetic isotope effect is probed (parallel measurement of rates vs. intermolecular competition vs. intramolecular competition), the observation of a primary kinetic isotope effect is indicative of breaking/forming a bond to the isotope at the rate-limiting step, or subsequent product-determining step(s).  (The misconception that a primary kinetic isotope effect must reflect bond cleavage/formation to the isotope at the rate-limiting step is frequently repeated in textbooks and the primary literature: see the section on experiments below.)
For the previously mentioned nucleophilic substitution reactions, primary kinetic isotope effects have been investigated for both the leaving groups, the nucleophiles, and the α-carbon at which the substitution occurs. Interpretation of the leaving group kinetic isotope effects had been difficult at first due to significant contributions from temperature independent factors. Kinetic isotope effects at the α-carbon can be used to develop some understanding into the symmetry of the transition state in S2 reactions, although this kinetic isotope effect is less sensitive than what would be ideal, also due to contribution from non-vibrational factors.