Sensitivity analysis aims at exploring which of a number of variables have an impact on a certain response. Not only are the individual variables of interest but also whether they interact or not. By analogy with the total sensitivity index, used to detect the most influential variables, a screening of interactions can be done efficiently with the so-called total interaction index (TII), defined as the superset importance of a pair of variables. Our aim is to investigate the TII, with a focus on statistical inference. At the theoretical level, we derive its connection to total and closed sensitivity indices. We present several estimation methods and prove the asymptotical efficiency of the Liu and Owen estimator. We also address the question of estimating the full set of TIIs, with a given budget of function evaluations. We observe that with the pick-and-freeze method the full set of TIIs can be estimated at a linear cost with respect to the problem dimension. The different estimators are then compared empirically. Finally, an application is given aiming at discovering a block-additive structure of a function, where no prior knowledge either about the interaction structure or about the blocks is available.