In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.