The effect of topical applications of crystalline lysine therapy on cutaneous herpes simplex virus (HSV) inoculations and subsequent dorsal root ganglia (DRG) infection was studied in male Hartley guinea pigs. Although HSV-I was recovered from the inoculated sites from all animals, the L-lysine-treated skin remained clinically normal, whereas untreated controls manifested clinical symptoms up to 3 days postinoculation (p.i.). However, cocultivation of DRG (C1-S1) indicated a selective tropism of infective particles to specific DRG in the groups treated with amino acids. In lysine-treated animals, HSV was recovered from a few DRG (T-12, T-13, and L-1) at 3 days p.i. and from DRG T-10 in leucine-treated controls; yet no HSV was recovered from DRG of untreated controls. These results suggest an immunomodulatory effect of L-lysine on inoculation site infections and the possible potentiation of subsequent DRG manifestation in amino-acid-treated animals.