The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.