We have studied the effects of recombinant human alpha A interferon (IFN) on the multiplication of Visna retrovirus in ovine cells. Pretreatment with IFN followed by continuous IFN treatment, drastically blocked the Visna virus induced cytopathogenic effect and the emergency of neoformed virions. Thus, virus yield and virus dependent reverse transcriptase activity were highly reduced in supernatant fluids. All these effects were accompanied by a strong inhibition of viral protein synthesis. In the light of these data, human IFN action on Visna retrovirus seems to be determined by a mechanism of action distinct from that described in the case of other Retroviridae.