Immune function in acromegalic patients has been poorly investigated. The aim of this study was to evaluate the main surface antigen clusters of circulating lymphocytes in acromegaly. One hundred patients with active acromegaly (55 women and 45 men, aged 20-70 yr) and 200 healthy subjects sex- and age-matched with the patients (110 women and 90 men, aged 20-70 yr) were enrolled in this study. All patients and controls were born and live in Southern Italy. No patient had received octreotide, bromocriptine or corticosteroids for at least 3 months before entering the study. The analysis of lymphocyte subset pattern was performed by flow cytometry and fluorescein isothiocyanate or phycoerythrin directly conjugated monoclonal antibodies specific for the cell surface antigen clusters (CD) representing T-cell population as a whole (CD3), T helpers (CD4), T suppressors (CD8), natural killer cells (CD16) and B-cell population as a whole (CD19). Acromegalics had significantly increased levels of CD3 (67.1+/-7.2 vs 64.3+/-8.8%; p=0.03) and CD4 (37.8+/-3.5 vs 36.4+/-4.3%; p=0.004) and decreased levels of CD8 (31.4+/-3.3 vs 33.7+/-8.2%; p<0.01) and CD19 (12.1+/-3.1 vs 15.2+/-5.1; p=0.01) without age-difference. The results of the current study demonstrate an increase in T-cell activity together with a decrease in B-cell activity in a very large series of patients with active acromegaly. These data further support the existence of abnormalities of the immune system in patients with chronic GH/IGF-1 excess.