AIM: To investigate the effect on intraocular pressure (IOP) and aqueous flare of topical applications of latanoprost and dipivefrin alone or combined. METHODS: 22 patients with open angle glaucoma or ocular hypertension were included in a 4 week open label study. Median age was 68 years (range 50-79). They were allocated to either 2 weeks' treatment with once daily evening administration of latanoprost monotherapy (50 micrograms/ml) or twice daily dipivefrin monotherapy (1 mg/ml), followed by 2 weeks' combination therapy with both drugs. RESULTS: Latanoprost alone reduced IOP from 19.3 (SD 1.4) to 14.8 (0.9) mm Hg (p < 0.01). Addition of dipivefrin caused a further reduction to 12.4 (0.9) mm Hg (p < 0.01 compared with latanoprost alone). In the group where the treatment started with dipivefrin IOP was reduced from 22.3 (1.2) to 18.4 (1.0) mm Hg (p < 0.01) and with the combination to 14.9 (0.9) mm Hg (p < 0.01). No change in aqueous flare was observed with either drug, alone or in combination. A slight increase in conjunctival hyperaemia was observed when the two drugs were combined. CONCLUSIONS: Latanoprost and dipivefrin have an additive effect on IOP and no clinically significant effect on the permeability to proteins of the blood-aqueous barrier. This implies that the two drugs can be a useful combination for the treatment of glaucoma.