The aim of this study was to investigate autonomic neuropathy, with and without oxygen therapy, in patients with chronic obstructive pulmonary disease (COPD). Four cardiovascular tests for autonomic function were used, and in addition, basal pancreatic polypeptide (PP) was measured. The following COPD patients were studied: 10 normoxemic (mean PaO2 10.9 +/- SD 1.1 kPa), 10 hypoxemic (PaO2 7.6 +/- 0.7 kPa before, and 10.6 +/- 1.4 kPa after 24 h oxygen therapy), and 6 hypoxemic on long-term oxygen therapy (LTOT) (PaO2 10.3 +/- 1.3 kPa before, and 7.0 +/- 0.8 kPa after 4 h of low dose or oxygen free interval). Twenty healthy age-matched subjects served as controls. In the individual tests the hypoxemic and the LTOT groups had a significantly decreased heart rate response to the Valsalva manoeuvre (ratio 1.23 +/- 0.17 and 1.12 +/- 0.07 versus control's 1.45 +/- 0.26 (p < 0.01 and 0.005, respectively) and versus the normoxemic group 1.46 +/- 0.30 (p < 0.05)) and the hypoxemic as well as the LTOT group had a significantly decreased heart rate response to standing up (ratio 0.97 +/- 0.04 and 0.97 +/- 0.07, respectively, versus the controls 1.06 +/- 0.09 (p < 0.005 and 0.05)). The blood pressure response to standing up and to sustained handgrip did not differ significantly between the groups. In spite of apparent autonomic dysfunction, PP levels in the LTOT group were significantly higher than in the controls (p < 0.01-0.001) and the normoxemic group (p < 0.05-0.01). Twenty-four hours of oxygen treatment in the hypoxemic group or four hours of oxygen withdrawal in the LTOT group did not change the results significantly. In conclusion, our findings are consistent with the previous notion of neurological dysfunction from hypoxemia, but this may not be corrected by the use of short term oxygen treatment. This contrasts to previous findings in which longer term oxygen did correct some of these problems.