Determination of intraocular antibody synthesis against certain microorganisms is a diagnostic aid in identifying the causative agent in clinical uveitis. Little is known, however, concerning the kinetics and specificity of antibodies produced during intraocular inflammation. To investigate this subject we induced uveitis in rabbits by injecting small amounts of human serum albumin (HSA) into the vitreous. Aqueous humor and serum were taken before and after the induction of uveitis and levels of total IgG, rabbit albumin and anti-HSA-IgG were determined. The anti-HSA-IgG was quantitated using immunoaffinity purified anti-HSA-IgG as a standard. Six weeks after intravitreal HSA injection, high levels of total IgG (4.7 mg/ml) and albumin (15.4 mg/ml) were observed in the aqueous as compared to control eyes (IgG: 0.12 mg/ml; albumin: 0.48 mg/ml). Using albumin to correct for blood aqueous barrier breakdown we calculated that only 0.6% of the locally synthesized IgG was directed against intravitreally injected HSA. Two months after the intravitreal injection of HSA the main signs of the uveitis had subsided. A recurrent uveitis was subsequently induced by an intravenous HSA injection. This resulted in a marked increase of total IgG (14.3 mg/ml) and albumin (24.6 mg/ml) in the aqueous humor of the uveitis eyes. It was remarkable that the mean anti-HSA-IgG level (0.62 mg/ml) in the uveitis eyes was higher than that seen in serum (0.41 mg/ml). After this secondary uveitis, 9% of the locally synthesized antibodies were directed against HSA.(ABSTRACT TRUNCATED AT 250 WORDS)