Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent one of the body's primary lines of defense against viral infections, including herpes simplex (HSV). This immune defense system is negatively influenced by prostaglandins. A project was undertaken to evaluate the influence of an antiprostaglandin agent in vivo on these cytotoxic effects against cells infected with HSV. Thirteen subjects without previous histories of clinical herpes simplex infection were studied during menses with and without naproxen therapy. A statistically significant augmentation (p = 0.05) of natural killer-cell function was identified in mononuclear cells during therapy. Subjects with baseline cytotoxicity of less than 45% demonstrated consistent elevations during naproxen therapy. No other significant differences could be found for mononuclear or polymorphonuclear cells with regard to NKC and ADCC. There appears to be a subset of patients who may benefit from immunologic augmentation with antiprostaglandin agents when experiencing herpes simplex virus infection.