The simultaneous uptake of mannitol, a passive permeability marker, and the organic acid, p-aminohippuric acid, was measured in the anterior and posterior vitreous and retina. Uptake was determined in control, probenecid treated and streptozocin diabetic rats. The unidirectional influx, calculated as a 10 minute PS product for these compounds, was not increased by 2, 4, or 12 weeks of diabetes. A clearance value, calculated using an experimental time of 60 minutes was also examined in order to gauge efflux of these compounds from the eye. The 60 minute clearance value for mannitol in the retina increased approximately 75% in 2, 4, and 12 week diabetic rats. This was an unexpected result due to the lack of increase in the unidirectional flux of mannitol during these same periods of diabetes, and may represent a change in the passive efflux out of the retina. The 60 minute clearance value for mannitol was not significantly changed in either the anterior or posterior vitreous. Experimental diabetes increased the 60 minute clearance value for PAH for the retina by 40% to 70%. In contrast, diabetes did not increase influx of PAH into the anterior or posterior vitreous. Because the unidirectional influx of PAH into the retina was not increased during diabetes, a decrease in the active transport for organic acids out of the eye is a likely explanation for the increase in the 60 minute clearance value for PAH during diabetes.