In order to obtain a better understanding of immune system function in chronic alcoholism, we have assessed primary B-cell responses to helper T-cell independent (TI) and dependent (TD) antigens in chronic alcoholic Sprague-Dawley male rats fed totally liquid diet containing ethanol. Pair-fed littermates received the same diet except that carbohydrates isocalorically replaced ethanol, which accounted for 36% of the total calories. The ability of alcoholic animals to mount primary in vivo splenic plaque-forming cell (PFC) responses to TI pneumococcal polysaccharide type III (SIII) was elevated throughout 50 days of observation when compared to pair-fed controls; serum antibody responses to SIII paralleled the enhanced PFC responses. Primary in vivo B-cell responses to antigen sheep red blood cells (SRBC), a TD antigen, were initially elevated but were found to be significantly suppressed 30 days after chronic ethanol consumption. The degree of immunosuppression increased with length of chronic ethanol consumption. The elevated primary splenic PFC responses to TI (SIII) may be attributed to loss of T-suppressor cell control, since alcoholic rat spleen cells did not respond to low-dose priming with SIII. We suggest that either loss of function and/or actual depletion of accessory and regulatory cells (T-suppressor and T-helper) may be responsible for irregularities in B-cell function observed during chronic alcoholism. T-cell subset enumeration using fluorescein-labelled monoclonal antibodies revealed that a sequential T-helper and T-suppressor loss occurred several days following dysfunction of these T-cell subsets in splenic populations, suggesting that a combination of numerical and dysfunctional changes in lymphocyte subpopulations may be responsible for the immunological alterations observed in chronic alcoholics.