Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.