In the present study, [ 3 H]-candesartan binding experiments were performed on intact Chinese Hamster Ovary cells transfected with the human AT 1 receptor (CHO-AT 1 cells). Cells were pre-treated with 0.01mg/ml saponin or filipin. Both pre-treatments resulted in an increased dissociation rate and decreased affinity of the insurmountable non-peptide antagonist [ 3 H]-candesartan. A similar decrease in affinity was observed for the peptide antagonist Sar 1 -Ile 8 angiotensin II and for other non-peptide antagonists, irrespectively of their degree of insurmountability. A similar discrepancy in [ 3 H]-candesartan binding was earlier observed when comparing intact CHO-AT 1 cells and membrane preparations thereof. This similarity is further highlighted by the observations that saponin or filipin no longer affect [ 3 H]-candesartan binding to CHO-AT 1 cell membranes and that both agents permeabilise the CHO-AT 1 cells. This suggests that the intracellular composition and/or organisation of living cells play an active role with regard to antagonist-AT 1 receptor interactions.