Summary Flunarizine is a class IV calcium channel blocker which increases oxygen delivery to hypoxic regions in solid tumours, exerting a radiosensitising effect in vivo in animal tumour models. Precisely how the drug improves oxygenation is not well understood. We hypothesised that metabolic conditions present within solid tumours reduce red blood cell (RBC) deformability and that flunarizine exerts its in vivo effect by preventing this loss of RBC deformability. A al., 1991). Blood flow in tumour microvasculature involves complex interactions of cellular elements, variable pressure gradients, and irregular vessel morphology (Jain, 1988). However, in very small vessels and capillaries, the deformability of the individual erythrocyte (RBC) becomes increasingly more important as the discoid cell must fold over onto itself in order to navigate through passageways often smaller than its own diameter. Indeed, there exists direct evidence of the impact of altered RBC deformability on the apparent in vivo blood viscosity in tumour microcirculation. For example, Sevick and Jain have used hyperglycemia to induce slight cell volume changes which impair RBC deformability, thus causing measurable increases in the pressure gradient required for equivalent flow rates across tumour vascular beds (1991).An agent capable of improving the deformability of RBC's might be useful in the enhancement of radiosensitivity if there is reason to believe that loss of deformability selectively occurs within the environment of the tumour, thus compromising blood flow and oxygen delivery there. Prominent characteristics of tumour centres include significant hypoxia and the lactic acidosis which may result in such circumstances (Vaupel et al., 1989), and it has recently been confirmed by direct measurement that PO2 within flowing tumour vessels may be lower than 10 mmHg (Dewhirst et al., 1992a). It was our specific intention to determine whether such environmental conditions adversely affect the deformability of erythrocytes. Also, it was our goal to assess whether flunarizine has activity in these conditions in reversing any loss of RBC deformability.Flunarizine (E-1 -[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride) is a WHO class IV calcium-entry blocking agent which enhances radiosensitivity in vivo in animal models (Wood & Hirst, 1988). Numerous studies have demonstrated that the drug significantly improved blood flow and oxygenation in the hypoxic regions of tumours implanted experimentally in animals (Kaelin et al., 1984;Vaupel & Menke, 1987;Fenton & Sutherland, 1992