A new acyclic adenosine analogue, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was evaluated for its efficacy in the topical treatment of experimental keratitis caused by the thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simple virus type 1 (HSV-1) strains. In the treatment of TK+ HSV-1 keratitis, 0.2% (S)-HPMPA eyedrops were as effective as the reference compounds, 0.2% (E)-5-(2-bromovinyl)-2''-deoxyuridine (BVDU) and 0.2% 5-(2-chloroethyl)-2''-deoxyuridine (CEDU) eyedrops. The three compounds produced a statistically significant healing effect, as compared with placebo eyedrops. In the treatment of keratitis caused by the TK- HSV-1 strain, 0.2% BVDU and 0.2% CEDU eyedrops did not differ from placebo eyedrops, whereas 0.2% (S)-HPMPA eyedrops exerted a highly significant healing effect.