Experimental models have implicated glutamate in the irreversible damage to retinal cells following retinal detachment. In this retrospective study we investigated a possible role for glutamate and other amino acid neurotransmitters during clinical rhegmatogenous retinal detachment (RRD). Undiluted vitreous samples were obtained from 176 patients undergoing pars plana vitrectomy. The study group consisted of 114 patients (114 eyes) with a rhegmatogenous retinal detachment. Controls included 52 eyes with an idiopathic macular hole or idiopathic epiretinal membrane and 10 eyes with a traction retinal detachment due to proliferative diabetic retinopathy. Vitreous concentrations of glutamate, gamma-aminobutyric acid (GABA), taurine, glycine, and aspartate were determined by high-pressure liquid chromatography (HPLC). Multivariate analysis was used to examine a possible association between amino acid neurotransmitter levels and several clinical variables including visual acuity. The mean vitreous concentration of glutamate in eyes with a rhegmatogenous retinal detachment (16.6+/-5.6muM) was significantly higher as compared to the controls (13.1+/-5.2muM) (P=0.001). Taurine levels were also increased in RRD, whereas no significant difference could be observed in glycine, aspartate and GABA levels when comparing RRD with controls. A correlation was found between increased vitreous glutamate and a lower pre-operative visual acuity. No association was, however, observed between post-operative visual acuity and the level of any of the five amino acid neurotransmitters. RRD was associated with a significantly increased vitreous glutamate concentration. Using visual acuity as a functional parameter in this study, we could not demonstrate a correlation between vitreous glutamate, or any of the other tested amino acid neurotransmitters and visual outcome.