In vitro lymphocyte blastogenic responses to the commonly employed mitogens, phytohemagglutinin, pokeweed, and concanavalin A, were evaluated when adenine arabinoside (ara-A) in a concentration of 3 μg/ml was added to the culture materials. Similarly, blastogenic and cytotoxic responses to cell cultures persistently infected with herpes simplex virus 1, herpes simplex virus 2, and varicella-zoster virus were determined in the presence of ara-A. No depression of these cellular immune responses by ara-A was demonstrated. This was in contrast to the effect of cytosine arabinoside, which at a concentration of 3 μg/ml severely inhibited these immune responses. Further studies examined lymphocyte blastogenic responses to the mitogens and blastogenic and cytotoxic responses specific for the herpes group virus infecting patients who were subsequently treated with ara-A; determinations were made before, during, and after treatment. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared to pretreatment values. Therefore, the antiviral chemotherapeutic agent, ara-A, does not appear to depress the host's cellular immune responses, which are vital to successful elimination of invading herpes group viruses.