In four different groups of eight normal volunteers the intraocular (IOP) and episcleral venous pressures (EVP) were measured before, and at 7.5, 15, 30, 45, and 60 min after topical application of one drop of clonidine (1/4%), epinephrine (1%), or pilocarpine (2%) by means of applanation tonometry or the air-jet method, respectively. The results were compared with a control group. In the control group the IOP decreased by 16% until the fourth measurement. Subsequently it increased to -10% after 60 min. The EVP remained unchanged. After clonidine application the IOP decreased throughout the whole experiment (-31% after 1 h) and after the third measurement the IOP decrease was significantly more marked than in the control group. The EVP I diminished significantly during the first 15 min by 25% and then increased, reaching its initial value after 60 min. IOP and EVP I showed parallel behavior only during the first 30 min. Topical application of epinephrine was followed by a much smaller decrease in IOP (17% after 60 min); compared to the control group the differences were minor. The EVP I was reduced significantly by 15% below the initial level after 45 min while EVP and IOP behaved identically. After pilocarpine application the IOP rose initially (7% after 7.5 min) and decreased markedly after 10 min (33% after 1 h). Compared to the untreated volunteers there were significant differences at nearly all times. At the outset the EVP I increased significantly (29% after 7.5 min), and then decreased again until it regained the initial value after 30 min. Only at the beginning of the experiment were the reactions of IOP and EVP similar.