The action of glutamate in retina is largely terminated through rapid uptake by Müller cells and subsequent conversion primarily to glutamine. Glutamine, transferred from Müller cells to neurons, serves as a precursor for the formation of glutamate in neurons completing the glutamate-glutamine cycle. In a monkey model of high-tension glaucoma, we have examined glutamine immunoreactivity in the Müller cell as well as the number of Müller cells to determine whether the activity of these cells in the glutamate-glutamine cycle is affected, particularly since high vitreal glutamate has been reported in glaucoma. Unilateral glaucoma was induced in three monkeys by argon laser application to the trabecular meshwork. LR White sections of retina from the temporal mid-periphery (about 23 degrees) and the parafovea (central 3 degrees) were immunolabeled for glutamine using immunogold and silver intensification. The percentage difference in labeling intensity (darkness) in the glaucomatous retina was determined relative to the labeling found in the control retina by image analysis. Ganglion cell density was estimated from radial sections in the parafovea and from retinal whole mounts in the mid-periphery. The number of Müller cells was estimated from vibratome sections immunolabeled by vimentin antibodies in the temporal mid-periphery (about 30 degrees). Glutamine immunoreactivity was localized predominately in ganglion cells and Müller cells. However, the intensity of glutamine immunolabeling was greater in Müller cells of glaucomatous eyes than in control eyes. This increase in glutamine immunolabeling was 25-32% in the temporal mid-periphery and 27-48% in the parafovea. Müller cell number in the glaucomatous eye was similar to that of the control in the temporal mid-periphery. The data in this study indicate that the increase in glutamine in Müller cells is not a consequence of their loss and that Müller cell function in the glutamate-glutamine cycle continues in glaucomatous eyes. These findings are consistent with a previous report that extracellular/vitreal glutamate concentration is elevated in high-tension glaucoma.