Chronic alcoholics are frequently immunodeficient, have polyclonal hypergammaglobulinaemia, and often have autoantibodies. Recent work in other diseases has shown that functional distinctions of possible relevance to autoimmunity and immunodeficiency can be found among the B cell subsets defined by differential expression of the surface markers CD5 and CD45RA. Therefore, we have evaluated the CD5, CD45RA B cell subsets of both chronic alcoholics without evidence of active liver disease (AWLD), and alcoholics admitted for acute alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry in 20 patients and 29 controls revealed a sharp decrease in the percentage of alcoholics' B cells which were CD5+, 37.6% versus 16.3%, P < 0.000 01; absolute CD5+ B cell numbers were similarly reduced (58.9 cells/microliters versus 20.9; P = 0.0012). In addition to the loss of CD5+ B cells, there was a reduction in the percentage of B cells which are CD5- CD45RAhi, leaving many patients with a B cell profile which was predominantly CD19+ CD5- CD45RAlo. This subset appears phenotypically similar to the IgM-producing CD5- CD45RAlo subset described by others, and may be enriched for autoantibody-producing cells. One outlier patient was an ALD with 61% of B cells which were CD5+, which also is a profile consistent with increased autoantibody production.