Bolus intracameral infusion of 100 micrograms cAMP, corresponding to an initial intracameral concentration of 3 mM, significantly increased total outflow facility in cynomolgus monkey eyes with intact or disinserted-retrodisplaced ciliary muscles by 41% and 37% respectively. Lower cAMP doses had little or no effect in both types of eyes, as did dibutyryl cAMP doses of 1-100 micrograms (20 microM-2mM). In eyes with intact ciliary muscles, intracameral infusion (1 and 10 micrograms) of the cAMP analog 8-methylthio cAMP (0.25 mM and 2.5 mM) significantly increased facility by 55% and 69% respectively, while 100 micrograms of the inactive cAMP metabolite 5'AMP (3 mM) did not alter facility. The facility increases produced by cAMP and 8-methylthio cAMP represented a constant percentage of starting facility independent of the absolute value of starting facility. These findings indicate that the facility increase produced by cAMP and appropriate analogs is not mediated by ciliary-muscle contraction and that the disinsertion procedure itself does not compromise the ability of the outflow pathways to respond to cAMP. The facility increase probably represents a cAMP effect directly on the endothelial cells of the trabecular meshwork-Schlemm's canal inner wall.