As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon testp<0.05); (2) sertindole and clozapine significantly increased the mean resting heart rate; and (3) only clozapine significantly reduced the parasympathetic resting tone. The results of the HRV studies are discussed considering thein vitroreceptor profiles of the atypical neuroleptics under study. Potential implications for the cardiac safety and tolerance of these drugs are also discussed.