The finding of part of the Herpes simplex virus type 1 (HSV1) genome in peripheral blood leucocytes of some patients with Behcet's disease (BD) led to investigations of T cell responses to HSV1 in this disease. A significantly impaired uptake of 3H-thymidine by CD4 cells was found in BD, as compared with healthy HSV1 sero-positive subjects. The impaired cellular response appeared to be specific to HSV1, as neither cytomegalovirus nor varicella-zoster virus showed depressed CD4 cell responses in BD. A similar impairment of CD4 cell responses to HSV1 was found in patients with recurrent herpetic infections, known to be caused by latent HSV1 infections. However, in rheumatoid arthritis which was selected as an unrelated autoimmune disease. 3H-thymidine uptake by CD4 cells stimulated with HSV1 was enhanced. CD8 cells showed generally rather a low uptake of 3H-thymidine, nevertheless, the values in BD and recurrent herpetic infection were again lower than those in sero-positive controls or rheumatoid arthritis. The results are consistent with the hypothesis that HSV1 might be involved in the immunopathogenesis of BD.