The clinical significance of N-type calcium channel blockade has not been fully examined. We here compared the effects of the N-type calcium channel blockers cilnidipine and amlodipine on the sympathetic nervous system and platelet function in hypertension under resting and stressed conditions. Thirty-two patients with hypertension (58±9 years) received cilnidipine or amlodipine for 4 weeks in this crossover study. On day 28 of each treatment, plasma levels of epinephrine (EP), norepinephrine (NEP), and β-thromboglobulin (BTG), and EC₅₀ of ADP- induced platelet aggregation (ADPEC₅₀) were determined at rest and after a cold pressor test. On day 29, the group receiving cilnidipine was switched to amlodipine treatment, and vice versa. At rest, the blood pressure, heart rates, EP, NEP, ADPEC₅₀, and BTG, were similar in both treatments. After the cold pressor test, increases in EP (35±17 to 44±25 pg/ml; p<0.05) and BTG (40±13 to 49±22 ng/ml; p<0.01) and a decrease in ADPEC₅₀ (32±26 to 27±24 μmol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment. In addition, the increase in NEP was significantly greater (p<0.05) in the amlodipine (276±78 to 318±87 pg/ml; p<0.01) than in the cilnidipine treatment (273±88 to 291±100 pg/ml; p<0.05). Cilnidipine more highly attenuates the activation of platelet function in response to cold pressor stress then does amlodipine. Attenuated activation of the sympathetic nervous system via N-type calcium channel blockade may contribute to this phenomenon. (Hypertens Res 2001; 24: 679-684)