1. Neurogenic vasoactive responses in rat skin were investigated following 8 weeks of streptozotocin-induced diabetes to determine the effect of diabetes and of treatment with insulin and nerve growth factor (NGF) treatment. 2. Diabetic rats were divided into three groups: untreated; insulin (4 IU day(-1) by s.c. implant weeks 4-8) treated; Nerve Growth Factor, NGF, (0.2 mg kg(-1) three times weekly, weeks 4-8) treated. A fourth group served as a non-diabetic control. 3. Electrical stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 30 s) increased blood flow in the ipsilateral paw skin, as measured by laser Doppler flowmetry. The peak increase was similar between groups, but the time taken for flow to return to a steady baseline was significantly (P < 0.01) reduced in untreated diabetic rats, when compared with non-diabetic controls, but not significantly reduced in the insulin- or NGF-treated diabetic groups. 4. A second stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 5 min) produced plasma extravasation, measured by the extravascular accumulation of 125I-albumin, in the skin. Plasma extravasation was significantly attenuated (P < 0.001) in the untreated diabetic group, but not the insulin-treated group, compared to non-diabetic controls. Plasma extravasation was present, though reduced, in the NGF-treated group. 5. Plasma extravasation induced by intradermal injections of substance P with and without CGRP was similar in all groups indicating no decrease in vascular responsiveness to exogenously applied neuropeptides. The results suggest that release of neuropeptides is diminished in diabetes and that treatment with either insulin or NGF can restore neurogenic microvascular vasoactive responses towards normal.