Retroviruses isolated from avian, feline, murine and simian sources have been found to be inactivated and lysed by normal human serum. There is much evidence that complement is activated directly by retroviruses in the absence of antibody. Thus, human complement is thought to function as a natural defence mechanism against horizontal infection by retroviruses. Recently, a novel retrovirus, human T-cell leukaemia virus (HTLV), has been shown to be associated with adult T-cell leukaemia/lymphoma (ATL). A large number of healthy adults in south-west Japan, the West Indies and Africa carry antibodies against HTLV and these seropositive individuals are considered to be carriers of HTLV. Thus, horizontal spread of HTLV occurs frequently among humans. We set out to determine whether HTLV reacts with human complement, and report here that, unlike other animal retroviruses, HTLV is not lysed by normal human serum--this might explain the infectivity and persistence of HTLV in humans.