The lymphocyte transformation test was used to assess cell-mediated immune reactivity in 107 Ethiopian patients with syphilis. Lymphocytes from patients with early syphilis were unreactive to the Nichols strain of Treponema pallidum, which was in marked contrast to previous findings in similar patients in England. Lymphocytes obtained from patients with late syphilis, however, were reactive. The responses elicited by a strain of T. pallidum isolated from an Ethiopian with early syphilis did not differ from those with the usual Nichols strain. About half the patients with early syphilis who had received antibiotic treatment for 8 days showed an increase of lymphocyte reactivity towards T. pallidum, although responses to PPD and PHA were unchanged. Plasma from patients with syphilis was examined for its capacity to inhibit lymphocyte responses in vitro. Although plasma from people with late (cardiovascular) syphilis did not differ from controls, plasma from patients with early syphilis inhibited the responses of their own cells to both PPD and PHA. The inhibitory effect on PHA responses was abrogated after the patients had received antibiotic treatment for 1 week. The significance of the differences in lymphocyte reactivity observed between Ethiopians with syphilis and their counterparts in England is discussed with regard to a possible explanation of the differences in the natural history of the disease in the two countries.