Abstract Isobutylmethylxanthine (IBMX), a phosphodiesterase/adenosine receptor inhibitor, was combined with norepinephrine (nE), epinephrine (Epi) and isoproterenol, respectively, to evaluate their effect on intraocular pressure (IOP). Application of topical IBMX alone had no measurable effect on IOP. When IBMX was combined with nE or Epi the ocular hypotension in rabbits and beagles increased. The E max for nE alone was 2·9±0·4 mmHg, for Epi alone 7·3±0·5 mmHg and for isoproterenol alone 5·1±0·3 mmHg. The EC 50 was 0·2±0·05% (nE), 0·05±0·01% (Epi) and 0·00±0·001% for isoproterenol. When given in combination with 1% IBMX the E max for nE was 7·4±1·7 mmHg, for Epi 9·0±0·8 mmHg and for isoproterenol 6·1±0·3 mmHg. The corresponding values for EC 50 were 0·07±0·03% (nE), 0·02±0.006% (Epi) and 0·002±0·001% for isoproterenol. Combining 1% IBMX with 0·1% Epi increased the aqueous humour cyclic AMP-levels at 1, 3 and 5 hr in rabbits. The results of this study demonstrate that a phosphodiesterase/adenosine receptor inhibitor such as IBMX enhances the reduction in IOP induced by adrenergic agonists.