Rats fed excessive amounts of ethanol developed marked hematologic and immunologic changes. These included a reversal of the normal lymphocyte to granulocyte ratio in the peripheral blood, lower spleen and lymph node weights and a greatly reduced capacity to express normal cell mediated immune functions, based on poor lymphocyte reactivity in vivo, and in vitro to T and B cell mitogens and borrelial antigens shortly after primary immunization with the bacterial spirochete, Borrelia burgdorferi. Further evidence for impaired immune function caused by ethanol was based on little or no antibody response against Borrelia in rats following in vivo sensitization with B. burgdorferi incorporated in complete Freund's adjuvant. These findings provide substantial direct evidence strengthening the notion that high levels of ethanol ingestion adversely affect the host immune system and can interfere with the immune response to microorganisms.