This is a non-randomized exploratory study showing the sensitivity of neurophysiological parameters for autonomic side-effects during the application of antidepressant drugs. Inpatients on tricyclic antidepressants (TCA: amitriptyline or doxepine), inpatients on serotonine-reuptake inhibitors (SSRI: fluvoxamine or paroxetin) and a control group of healthy volunteers underwent neurophysiological examination. The treatment group was investigated after at least 7 days of continuous treatment with the final dose. Adjustment of the autonomic nervous system was studied, first, by measuring latency and amplitude of the sympathetic skin response (SSR), elicited by electric stimuli and by deep inspiration, and second, by analysis of the heart rate variation (HRV) during rest and inspiration. Relevant affections of the peripheral parts of the reflex arc under discussion were excluded by taking the nerve conduction velocity (NCV) and F-wave referring to cervical segment C7. In total, 48 individuals were examined. The TCA group showed delayed latencies and smaller amplitudes of the SSR in comparison with the controls. In the SSRI group, these parameters did not differ significantly from those of the controls. Analysis of HRV put further emphasis on the impaired adjustment of the autonomic nervous system in the TCA group. To sum up, our test battery indicated a specific vegetative alteration due to TCA.