The effect of intraocular pressure (IOP) on retrograde axonal transport of horseradish peroxidase (HRP), from the geniculate body to the retina, was studied in the rat in vivo. In 2-hr experiments (17 eyes at 50 mmHg; 13 eyes at 15 mmHg), the pressures were set just prior to the expected HRP arrival into the eyes. In 4.5-hr experiments (24 eyes at 50 mmHg; 21 eyes at 15 mmHg), the pressures were set 2.5 hr before expected HRP arrival. HRP was measured in the retinas 5 hr after the intrageniculate injection. Transport blockage occurred at an IOP of 50 mmHg in both series of experiments. In an earlier study of axonal transport in vitro, an IOP of 50 mmHg also blocked retrograde HRP transport. In a third series of experiments, 15 eyes were set at an IOP of 180 mmHg for 10 min, 10-20 min before expected arrival of HRP into the eye, while 17 control eyes were set at 15 mmHg. After the 10 min, both groups of eyes were set at 15 mmHg for another 2 hr and the HRP content in the retinas measured, 5 hr after HRP injection. There was no significant difference between these two groups of eyes, suggesting either no rapidly occurring block or a rapid recovery of transport after the high-pressure period. It is proposed that optic nerve fibers are stretched and narrowed near or at their exit, by the high IOP, but recover their shape soon after IOP is normalized.(ABSTRACT TRUNCATED AT 250 WORDS)