The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and alpha-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-alpha-methylepinephrine (DP alpha meE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DP alpha meE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DP alpha meE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DP alpha meE was more rapid (35-45 min) when compared with DPE (1.5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DP alpha meE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DP alpha meE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DP alpha meE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional alpha-adrenoceptors. It is concluded that DP alpha meE is a potent adrenergic ocular hypotensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)