Cardiac adverse events in patients treated with atypical antipsychotics have gained increasing interest in recent years. In the present study, heart rate variability (HRV), which is a sensitive parameter reflecting central autonomic cardiac control, was investigated during treatment with olanzapine. Ten physically healthy male patients with schizophrenia, who displayed predominantly negative symptoms, were studied in the sleep laboratory under drug-free baseline conditions and after 4 weeks of olanzapine medication. HRV was assessed during different sleep stages both in the time and frequency domains. Only slight changes in HRV were shown during treatment, and appeared to be independent of sleep stages. Spectral analysis indicated a slight shift of the sympathovagal balance in favour of the sympathetic tone, which was consistent with an elevation of heart rate in the time domain; total HRV was not altered. These changes are in accordance with olanzapine's receptor profile exerting anticholinergic and anti-adrenergic properties. In conclusion, taken together with findings from previous studies demonstrating that olanzapine does not cause clinically significant changes of the QTc interval, the present results are consistent with the known cardiac safety profile of olanzapine.