Mean values and the spectral variability of heart rate (HRV), blood pressure, and skin blood flow were studied in high and low hypnotizable subjects during simple relaxation. Similar subjective relaxation was reported by highs and lows. A parasympathetic prevalence (indicated by a higher High-Frequency component of HRV and a lower High/Low-Frequency ratio) and lower renin-angiotensin activity (indicated by a lower Very-Low-Frequency component of HRV) could be attributed to highs with respect to lows. Hypnotizability did not affect blood pressure and its variability and modulated the skin blood flow across the session only in lows. The findings confirm that relaxation cannot be defined solely on cardiovascular parameters and also indicate that hypnotizability modulates cardiovascular activity during simple relaxation and suggest it may have a protective role against cardiovascular disease.