Intradermal injection of 0.5 microgram histamine produced equal skin reactions in normal individuals (n = 15) and in diabetic patients with (n = 10) or without (n = 9) evidence of autonomic neuropathy as well as in patients after lumbar sympathectomy (n = 5). Addition of noradrenaline (0.1 microgram) resulted in a significantly smaller skin reaction (mean +/- SEM) in normal (101.9 +/- 10.1 vs. 136.3 +/- 6.5 mm2, p less than 0.005) and in diabetic patients without autonomic neuropathy (101.8 +/- 8.4 vs. 123.9 +/- 8.7 mm2, P less than 0.05), but remained unchanged in diabetic patients with autonomic neuropathy (131.0 +/- 9.0 vs, 130.7 +/- 8.2 mm2, n.s.) and after lumbar sympathectomy (135.2 +/- 17.5 vs 130.2 +/- 19.6 mm2, n.s.) when compared with the reaction to histamine alone. Addition of terbutaline produced similar results as observed with noradrenaline. These findings suggest a defect at the adrenoceptor level in diabetic patients with autonomic neuropathy and in patients with lumbar sympathectomy. Thus, the combined intradermal injection of histamine and the adrenoceptor agonists noradrenaline or terbutaline represents a simple and useful test for identifying patients with impaired adrenergic function.