To the Editor: In an interesting and important report in the February 11 issue, Crumpacker et al.1 described the isolation of acyclovir-resistant herpes simplex virus from a patient treated with this promising antiviral agent. The virus induced less thymidine kinase activity than previous isolates from the same patient had induced, and the authors concluded that the resistance to acyclovir was due to the selection of herpes simplex virus deficient in viral thymidine kinase.Although the authors' conclusion could certainly be the correct interpretation of their data, there are several precedents for other plausible interpretations, such as altered thymidine kinase-substrate specificity . . .