A series of 9-benzyl-6-(dimethylamino)-9H-purines and 9-benzyl-2-chloro-6-(dimethylamino)-9H-purines were synthesized and tested in cell culture for activity against rhinovirus type 1B. The 9-benzylpurines that were unsubstituted in the 2-position had weak activity. However, introduction of a 2-chloro substituent resulted in a substantial increase in antiviral activity. One of the most active compounds, 2-chloro-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purine (29), had an IC50 value of 0.08 microM against serotype 1B. Four compounds were tested against 18 other rhinovirus serotypes, but the majority tested were less sensitive than type 1B. The range of serotype sensitivity for 29 varied from 0.08 to 14 microM. These 9-benzyl-2-chloro-9H-purines represent a new class of antiviral agents with in vitro activity against rhinoviruses.