The effects of timolol and betaxolol were compared for blocking beta agonist stimulation of cyclic-AMP in cultured human trabecular meshwork cells. Epinephrine (10(-5) M) produced a large and rapid increase in HTM cyclic-AMP; timolol (10(-6) M), at concentrations readily achieved in the aqueous humor after 0.5% eyedrops, completely blocked this effect. Recovery from timolol treatment appeared to be relatively slow, with only a 30-40% recovery observed by 9 hours. In comparison, betaxolol (10(-6) M) produced a smaller blockade of the epinephrine effects; a rapid recovery from the betaxolol effects was observed, with a greater than half-maximal response to epinephrine observed 15 minutes after removal of this beta blocker. These findings may help to explain the clinical observations of an outflow facility effect of epinephrine when used in combination protocols with betaxolol, but not with timolol.