Restriction endonuclease digestion of viral DNA has been demonstrated to be a sensitive technique for typing and for detecting different strains from the two subtypes of herpes simplex virus (HSV)[1-4]. Buchman et al. described two patients (of eight studied) from whom genital HSV-2 isolates obtained 3 and 10 months apart varied in their Kpn-I digestion patterns, an observation which suggests that these two patients had acquired exogenous reinfection with a new viral strain [I]. To evaluate the frequency of exogenous reinfection among patients with frequently recurring symptomatic genital herpes, we subjected sequentially obtained isolates to restriction endonuclease digestion. In order to optimize the likelihood of demonstrating exogenous reinfection with new strains of HSV, we selected for analysis only those patients in whom reinfection occurred and who also reported new sex partners during the interval between obtaining the sequential HSV isolates. Twentythree patients whose first genital HSV isolate was ob-