We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or a-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohe-magglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+cells in culture and interleukin (1L)-lα, IL-2, IL-4, tumor necrosis factor (TNF)αand soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+and CD8+T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+and PCAl+B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together. CD4+T cells were reduced in number in 9 cases, while CD8+T cells were reduced in 6 cases. The percentage of CD5+B cells was increased in 5 cases. The percentage of PCAl+cells was increased in all cases (mean±sd: 18±22 vs 0,2±1 in controls). The average PBL proliferative response to PHA was reduced (S.I. 71±55 vs 138±45 in controls) as well as that to PWM (S.I. 27±21 vs 75±24 in controls), despite IL-2 high levels, in all cases, in both sera (meanfsd: 648±351 pg/ml vs 16±4 pg/ml in controls) and culture supernatants (meanksd: 1045 f 677 pg/ml vs 195±51 pg/ml in controls). In PHA stimulated cultures the percentage of CD25+cells was reduced (meanasd: 37±18 vs 63±14 in controls), sIL-2R levels were like controls in 7 cases. In sera sIL-2R levels were increased in all cases (meanfsd 1256±465 U/ml vs 256±114 U/ml in controls), IL-lαwas increased in all cases too, while IL-4 levels were increased only in 7 cases. Linear regression analysis generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels in supernatants of PHA stimulated culture as well as between S.I. and the percentage of CD25+cells. Taken together these data suggest a state of B- and T-cell hyperactivation in AIHA. The low PBL proliferative responsein vim, explained in previous studies as a temporary functional exhaustion, might be itself a sign of the complete lymphocyte activation occurringin vivoin AIHA.