Levels of cAMP (23.1 pmol/ml) and cGMP (22.6 pmol/ml) are nearly equal in normal rabbit vitreous, although aqueous cAMP levels (29.9 pmol/ml) are 10 times higher than aqueous cGMP levels (2.6 pmol/ml) (P < 0.01). Intravitreal cAMP values decrease slightly 1 week after vitrectomy and lensectomy and return to normal whether the retina is attached, detached, or surgically removed. In contrast, intravitreal cGMP levels are profoundly depressed at 7 days (approximating normal aqueous levels) and are more than 50% lower than normal 30-42 days after surgery. The presence of these cyclic nucleotides in intraocular fluid and their responsiveness after surgery may signify a potential regulatory role in the physiologic responses of the eye to retinal detachment and its repair.