Background To test whether saw palmetto extracts, which act as α1‐adrenoceptor antagonists in vitro, also do so in vivo in man. Methods In a placebo‐controlled, double‐blind, four‐way cross‐over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human α1‐adrenoceptor subtypes. Results Saw palmetto extract treatment did not result in α1‐adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. Conclusions Despite their α1‐adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause α1‐adrenoceptor antagonism in man in vivo. Prostate 46:226–232, 2001. © 2001 Wiley‐Liss, Inc.