The effects of strepozotocin (STZ)-induced diabetes on the spontaneous peristaltic contractions in the upper urinary tract (UUT) of the rat were examined by simultaneously recording the tension in the proximal and distal regions of the renal pelvis and the proximal ureter. All regions of the UUT of diabetic rats contracted at a frequency similar to the contraction frequency of age-matched control rats. In contrast, contraction amplitudes in the proximal and distal renal pelvis and ureter of diabetic rats were 36%, 135% and 121% larger than the equivalent contractions recorded in control rats resulting in a significant increases in the motility index (MI amplitude x frequency) in all 3 regions. Capsaicin (10 μM), substance P (SP 2 μM) and neurokinin A (NKA 2 μM) caused a transient increase in MI in both control and STZ-induced diabetic rats. The rise in basal tension in the proximal and distal renal pelvis evoked by capsaicin, SP or NKA was also significantly greater in the diabetic rats when compared with controls. In contrast, human calcitonin-gene related peptide (hCGRP) produced a relatively small transient inhibition of UUT motility which was little affected by STZ treatment. These results suggest that capsaicin predominantly releases tachykinins from intrinsic sensory nerves in both non-diabetic and STZ-induced diabetic rats. We speculate that the supersensitivity of the diabetic UUT to capsaicin, NKA and SP 8-10 weeks after STZ treatment could be arising from an earlier development of sensory neuropathy.