The concentrations of substance P (SP) and vasoactive intestinal polypeptide (VIP) were determined in plasma in normal volunteers during acute occlusive ischaemia (n=5) and in patients with chronic ischaemia (n=5) due to obliterative arterial disease in the lower limbs. Venous SP, but not VIP, increased significantly in the early post-occlusive period in normal volunteers (P less than 0.02). In the patients no significant veno-arterial difference in plasma concentration of SP or VIP could be detected across normal or chronic ischaemic areas. The results may suggest a role for SP in the acute post-occlusive vasodilation and/or in the post-occlusive heat-pain sensation. A role for SP in chronic ischaemia could not be defined. Plasma VIP was unchanged in both acute and chronic ischaemia.