The combined effects of high pressure (up to 300 bar) and a homologous series of 1-alkanols (ethanol C2 to 1-tridecanol C-13) were studied on the main phase-transition temperature of dipalmitoylphosphatidylcholine (DPPC) vesicle membranes. It is known that short-chain alkanols depress and long-chain alkanols elevate the main transition temperature. The crossover from depression to elevation occurs at the carbon-chain length about C-10-C-12 in DPPC vesicle membranes coinciding with the cutoff chain-length where anesthetic potency suddenly disappears. Alkanols shorter than C-8 linearly decreased the transition temperature and high pressure antagonized the temperature depression. Alkanols longer than C-10 showed biphasic dose-response curves. High pressure enhanced the biphasic response. In addition, alkanols longer than the cutoff length depressed the transition temperature under high pressure at the low concentration range. These non-anesthetic alkanols may manifest anesthetic potency under high pressure. At higher concentrations, the temperature elevatory effect was accentuated by pressure. This biphasic effect of long-chain alkanols is not related to the 'interdigitation' associated with short-chain alkanols. The increment of the transition temperature by pressure was 0.0242 K bar-1 in the absence of alkanols. The volume change of the transition was estimated to be 27.7 cm3 mol-1. This value stayed constant to the limit of the present study of 300 bar.