We studied, using anesthetized albino rabbits, whether polymodal receptors are responsible for rise in the intraocular pressure (IOP) caused by algesic substances, and also whether substance P (SP) is involved in this phenomenon. Intracameral administration of bradykinin (BK), SP, hypertonic saline, and hypertonic glucose caused an IOP rise. The IOP responses to BK and hypertonic saline were reduced by benoxinate, but aspirin reduced only the response to BK. Repeated applications of BK caused a decrease in subsequent responses (tachyphylaxis). These results are consistent with the characteristics of responses of polymodal receptors, and suggest that these IOP responses are produced by neurogenic inflammation. The IOP response to SP also showed tachyphylaxis, but after the tachyphylaxis to SP had been established, subsequent intracameral administration of BK still produced a marked rise in IOP. Moreover, the administration of SP into the posterior chamber, which is known to be the site of the blood-aqueous barrier, caused a much smaller rise in the IOP. These observations indicate that the IOP response to algesic substances might be caused by activation of the polymodal receptors, and that SP might not be a mediator in these responses.