The amount of 9-beta-D-arabinofuranosyladenine (ARA-A) and 9-beta-D-arabinofuranosylhypoxanthine (ARA-Hx) present in ocular tissues of rabbits was determined following therapy with ARA-A alone and when ARA-A was used in combination with 2'-deoxycoformycin (dCF). Topical therapy was initiated three days after infection of the corneas of rabbits with herpes simplex virus type 1. Ocular tissues were harvested after two days of therapy and analyzed by high performance liquid chromatography. Combination topical therapy with ARA-A and dCF significantly increased the tissue content of ARA-A in all tissues examined except retina, as compared to therapy with ARA-A alone. The ARA-A content of the two ocular tissues most often subject to acute herpes infections, the conjunctiva and cornea, was increased from 29.9 +/- 11.7 to 144.0 +/- 53.3 pmoles/mg dry weight and from 15.4 +/- 6.1 to 231.8 +/- 30.8 pmoles/mg dry weight, respectively. Except for the aqueous humor, the total arabinoside content of each tissue was not significantly altered by combination therapy, merely the ratio of ARA-A to ARA-Hx was changed. These studies demonstrate that combination topical therapy with ARA-A and an inhibitor of ARA-A catabolism, dCF, can effectively result in elevated amounts of ARA-A in ocular tissues.