The present study examined the antiherpetic effect of 2′-nor-cGMP, a new cyclic phosphate derivative of 2′NDG,in vitroand in the mouse keratitis model. The 50% inhibitory dose (ID50) was determined with HSV-1 RE strain in Vero cell monolayers for 2′-nor-cGMP (6.9 mcg. /ml), 2′NDG (.06 mcg/ml), and trifluridine (F3T) (.72 mcg/ml). Balb C mice underwent bilateral ocular inoculation with HSV-1 RE strain, and then were treated with different therapeutic regimens. The antiviral efficacy of each drug was evaluated by ocular virus titers, clinical grading of epithelial keratitis, and histological evaluation of stromal keratitis. 2′-nor-cGMP was the most effective drug (P=. 0001) in reducing ocular viral titers. Both 2′-nor-cGMP and 2′NDG were significantly more effective (P=.000D than F3T in reducing epithelial keratitis, and as effective as F3T in reducing stromal keratitis.