OBJECTIVE: To examine the degree, pattern, and natural history of cardiac autonomic nervous dysfunction in patients infected with HIV. DESIGN: Cross-sectional and prospective longitudinal cohort study. SETTING: Primary care and tertiary referral university centre. PARTICIPANTS: Thirty-five consecutive HIV-infected patients who had either not yet developed AIDS (15 pre-AIDS patients) or who were at the Centers for Disease Control and Prevention (CDC) AIDS stage (n = 20), and 29 healthy age- and sex-matched HIV-negative controls. METHODS: Computer-aided power spectral analysis of 15 standardized parameters of heart-rate variability (HRV). RESULTS: Pre-AIDS patients as a group did not exhibit any HRV parameters to be significantly different from healthy controls (P > 0.017), whereas AIDS patients demonstrated reduced HRV in 14 parameters (93.3%) compared with healthy subjects (p > 0.017). Median proportion of abnormal HRV parameters (< 10th percentile of controls) per individual was 9.1% in pre-AIDS patients and 61.3% in AIDS patients (P = 0.0347). Progressive CDC stages inversely correlated to 10 HRV parameters (66.7%; -0.50 < or = r < or = -0.36; P < 0.05). Follow-up testing in 10 pre-AIDS and six AIDS patients after 6-16 months (median, 12.5 months) did not reveal deterioration of HRV (P < 0.05). A dysautonomia symptom score correlated to 10 HRV parameters (66.7%; -0.14 < r < -0.55; P < 0.05). CONCLUSIONS: Cardiac autonomic nervous dysfunction is severe in AIDS patients, although not significant in pre-AIDS patients. Cardiac autonomic nervous dysfunction proceeds with HIV disease progression, although its individual course is slow.