As recently shown, the measurement of labile disulfide bonds and free thiol groups of human IgG using 5,5′-dithio(2,2′-dinitro)benzoic acid (DTNB) provides direct information about the relative concentrations of IgG1 and IgG2, respectively. Furthermore, using this technique data have been obtained that show a decrease in labile S-S (corresponding to IgG1) and increase of free SH (corresponding to IgG2) in IgG from patients afflicted with various malignant diseases. In the present study a total of 280 sera from patients with malignancies of various tissue origin was investigated. Significantly reduced ΣS values, i.e. the sum of free SH and labile S-S, were obtained with IgG from cases of carcinoma of the mammary gland, urinary bladder, skin and prostate, as compared to cases with benign diseases of the respective organs. Most pronounced differences were observed between benign and malignant disorders of the prostate. It was confirmed with this group of patients that the reduction of ΣS was due to the decrease of S-S bonds, whereas the number of free SH groups remained unchanged or was increased. The cases of mammary gland carcinoma were grouped according to clinical stage. A clear correlation between reduction of ΣS and tumor size was observed. The possible theoretical and clinical implications of these results are discussed.