A set of nine 4-phenyldihydropyridine (DHP) calcium-channel blockers including both ionizable and unionizable molecules has been examined. The chromatographic parameters log k' have been determined by HPLC on an immobilized artificial membrane (IAM) column which is a solid-phase model of fluid membranes. The influence of different percentages of organic modifier and ionic strength of the eluent on the chromatographic behaviour has been studied in order to identify the best experimental conditions modelling the in vivo interaction with phospholipids. As different ranking orders can occur under different experimental conditions, log k' values extrapolated to 100% aqueous phase (log k I A M w ) have been determined. Moreover,n -octanol/buffer partition data at pH 7.4 and 12.5 (log D 7 . 4 and log P) and chromatographic data on a hydrocarbon HPLC stationary phase (logk O D S w ) have been measured. Comparative studies between the experimental data, obtained for the different systems, have shown that the IAM-derived scale is distinct from the one obtained by 'conventional' lipophilic indices, because of the particular behaviour of the basic DHPs. Moreover, only IAM parameters are good descriptors of the strong interactions of the basic DHPs with biomembranes. In fact, the chromatography of neutral compounds is mainly lipophilicity dependent while a 'dual' mechanism, partition and ion-exchange, operates for basic analogues. In this case the lipophilic component is insensitive to the protonation of the basic function. Finally, receptor binding values from rat cortical brain preparations successfully correlate with log k I A M w . Hence, the biomembrane affinity of DHPs appears to be a critical factor for access to their receptor site.