Our findings represent additional arguments to further evaluate the usefulness of individualising imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients. In CML, no straightforward concentration–response relationships were obtained. Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6☑.1 P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). odds ratio 2.7☐.6 for a two-fold free AUC increase in GIST P<0.001). Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. Influence of KIT genotype was also assessed in GIST patients. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha 1-acid glycoprotein. Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST).