The frequencies of HLA-A, B, C, DR, and DQ lymphocyte alloantigens were determined in 31 Sicilian patients with recurrent herpetic lesions (RHL) and compared to frequencies observed in normal individuals. A significant negative association was found for HLA-B35 (pc = 0.049). The relationships between HLA and immune responses to viral infections are discussed in light of the results revealed by the present investigation suggesting that HLA-linked genetic factors may play a role in the pathogenesis of RHL. The results seem to indicate that genes in the major histocompatibility complex (MHC) are influential against developing RHL.