Substance P (SP)-immunoreactive fibres have been found in the rat and guinea-pig irides. They are distributed parallel to the pupillary margin in the sphincter muscle, and in an irregular plexus in the dilator muscle of both species. Neuropeptide Y (NPY)-immunoreactive fibres have also been demonstrated in the anterior uvea, displaying a pattern similar to that of the adrenergic nerves. One month after sympathectomy, there was an increase both in the density and possibly in the number of SP-immunoreactive fibres in the denervated irides of both rodent species. In the sympathectomized iris, there was a very notable decrease in the density of NPY-immunoreactive fibres indicating that the NPY peptide most likely coexists with the classical sympathetic neurotransmitter, noradrenaline, in the sympathetic nerve supply derived from the superior cervical ganglion. The disappearance of dopamine beta-hydroxylase (DBH) immunostaining fibres confirmed the success of the sympathetic denervation.