The effect of treatment of an existing neuropathy in streptozocin-induced diabetic rats with the ACTH4-9 analogue ORG 2766 was examined. Four groups of rats were studied: group 1 consisted of age-matched, non-diabetic controls and groups 2, 3 and 4 of diabetic rats. Sensory and motor nerve conduction velocity (SNCV and MNCV) were measured at weeks 0, 4, 6, 8 and 10. Four weeks after the administration of streptozocin (STZ) all diabetic rats showed a significant slowing of SNCV and MNCV. Treatment was then started: group 2 was treated with placebo, group 3 with a low dos (1 microgram) of ACTH4-9 subcutaneously every 48 h, and group 4 with a high dos (10 micrograms) of ACTH4-9 subcutaneously every 48 h. The animals treated with the high peptide dosage showed a significant improvement in both SNCV and MNCV from week 6 onwards, whereas this beneficial effect was not demonstrated for the rats treated with the low dosage. This study demonstrates that the ACTH4-9 analogue ORG 2766 can ameliorate existing diabetic neuropathy in STZ-induced diabetic rats.