Cardiovascular autonomic function tests were performed in 24 patients with sickle cell anemia (SCA). Twenty-five healthy Afro-Caribbean black subjects and 38 healthy white subjects of Hispanic origin served as controls. Measurements based on heart rate variability (HRV) included the coefficient of variation (the standard deviation of the distribution of R-R intervals divided by the mean) and spectral analysis (low- and high-frequency bands) at rest, HRV during deep breathing (expiration-inspiration difference), Valsalva maneuver (Valsalva ratio) and lying-to-standing test (30:15 ratio). Fourteen patients (58.3%) were found to have cardiovascular autonomic dysfunction based on abnormal values for at least two cardiovascular autonomic function tests, whereas ten (41.7%) had preserved cardiovascular autonomic function. In contrast, all control subjects had normal cardiac autonomic function. SCA is known to be associated with sudden death. Involvement of autonomic nervous dysfunction in sudden death has been reported in various diseases and we suggest that this may be the case in SCA.