The lipophilicity (expressed by log P(oct)) and H-bond donor acidity (expressed by DELTA-log P(oct-hep)) of the dopaminergic agonist piribedil in different ionization states were investigated in order to assess its capacity for crossing membranes. The present study showed that piribedil has a relatively high lipophilicity (log P(oct) = 2.84) and is a non- or very weak H-bond donor (DELTA-log P(oct-hep) = 0.75), implying optimal properties for transmembranal transport. Based on its microscopic ionization behaviour as studied by C-13-NMR spectroscopy and (log P - log P+) value (5.04) (a measure of the stability of the ionic vs neutral species in a lipidic phase), protonation proved to be very unfavourable in water-saturated octanol due to the hindrance of solvation by the two bulky groups adjacent to the piperazinyl amino group. In addition, transport of piribedil across a lipophilic membrane was studied according to first-order kinetics in a three-compartment model. The effects of lipophilic counterions on the partitioning behaviour and transfer kinetics were examined and shown to be non-existent at equimolar concentrations