['Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent.', 'We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 +/- 4 years) and 12 young (29 +/- 4 years) habitual smokers matched for body mass index (25 +/- 2 kg/m2 in both groups).', 'Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 +/- 3 versus 12 +/- 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 +/- 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 +/- 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 +/- 2 bpm) was greater than that seen in middle-aged subjects (13 +/- 2 bpm, P < 0.01).'] Are sympathetic neural responses to smoking age dependent?