Objective HLA antigens influence tumour growth and spreading, but the mechanism is still unclear. Increased serum levels of beta 2-microglobulin (beta 2MG) have been found in several chronic inflammatory and tumour diseases. The aim of the present study was to analyse the relationship between serum beta 2MG levels and some markers of tumour progression, to verify the reliability of this parameter as a marker of hepatocellular carcinoma (HCC) progression, Design We studied 50 patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by chronic hepatitis C and 20 healthy controls. We performed a statistical analysis on the data obtained from haematological withdrawals in patients and healthy subjects. Methods Serum beta 2MG levels were determined by an immunoturbidimetric method (normal values range from 0.8 to 27 mu g/ml). Diagnosis of HCC was performed on the basis of haematochemical parameters (alpha-fetoprotein) and instrumental examinations (ultrasonography and computed tomography). In order to perform the statistical analysis we used the Wilcoxon non-parametric rank test and the Spearman log-rank correlation test Results Patients with HCC showed higher serum beta 2MG levels than did chronic hepatitis C patients (36 +/- 16.5 mu g/ml versus 2.3 +/- 0.8 mu g/ml; P < 0.0001) or healthy subjects (36 +/- 16.5 mu g/ml versus 1.6 +/- 0.4 mu g/ml; P < 0.0001), We found a positive correlation between beta 2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta 2MG and alpha-fetoprotein (r = +0.4; P = 0.005), beta 2MG and tumour size (r = +0.3; P = 0.02). Conclusions An increase in the beta 2MG serum level reflects the tumour size and seems to be a consequence of the stimulation on hepatocytes by humoral components of immunological response, such as IL-6. Weakening of the immune system, due to IL-6, may be responsible for a more severe progression of HCC and the hyperexpression of beta 2MG, (C) 2000 Lippincott Williams & Wilkins.