The objective of this study was to examine whether vegetative cardiac innervation is affected by local application of botulinum toxin A and B. For that purpose, heart rate variability (HRV) was measured in 29 patients treated with botulinum toxin A and 26 patients treated with botulinum toxin B both prior to and three weeks following injection. Among the 14 parameters studied, 9 and 10 had significantly changed in terms of decreased HRV following treatment with botulinum toxin A and B, respectively. Obviously, either type of botulinum toxin exerts a systemic effect, although a clear-cut difference between the two preparations was undetectable. By and large, the changes observed tend to be low compared to, for instance, cardiac effects known to occur with tricyclic agents. However, the results might be of relevance for the use of botulinum toxins in patients with a history of cardiac disease since a reduction in HRV correlates with an increased incidence of cardiovascular events. Therefore, an ECG study is advised prior to onset of therapy with botulinum toxin. In addition, nonjudicious use of botulinum toxin outside a defined range of medical indications should be reassessed.