sHLA are soluble forms of class I histocompatibility antigens detected in human serum and cerebrospinal fluid. These molecules are secreted by B and T lymphocytes and the secretion increases dramatically upon mitogenic activation of these cells. sHLA was quantified by an ELISA sandwich method in sera from healthy blood donors, and from patients with Non Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD) both at diagnosis and at remission. Pretreatment sHLA serum levels in NHL and in HD were compared with the values found in controls. sHLA levels are increased in patients with NHL (low grade: 6.68 +/- 1.80; high grade: 2.65 +/- 0.53 microg/ml X +/- S.E.) and HD (6.44 +/- 0.98) at diagnosis and in relapses when compared with controls (0.89 +/- 0.08). This increment is statistically significant (low grade NHL: p = 0.0038; high grade NHL: p = 0.0049 and HD: p = 0.0005 versus control group). No statistical differences between titers of sHLA after complete remission and sHLA in the control group were found. The high levels of sHLA detected in patients with lymphoma are mainly due to low molecular weight HLA molecules (55 KD) (60-75% of the HLA present in serum in the control group and 75-100% in serum of patients with lymphoma).