In order to evaluate the changes in humoral immunity due to one and two atherogenic factors (systemic hypertension and/or diabetes mellitus), we investigated 350 women divided into four groups: (1) 65 insulin-dependent (type I) non-hypertensive diabetics; (2) 92 systemic hypertensive non-diabetic subjects; (3) 64 hypertensive insulin-dependent diabetics; and (4) 129 non-hypertensive and non-diabetic women as a control group. All subjects had no coronary artery disease. The humoral immunity was evaluated by (1) circulating immune complexes, (2) total serum complement, (3) C3 fraction of complement, and (4) circulating antitissue antibodies (antivascular and antisclerotic-vascular). The patients with atherosclerotic risk factors (diabetes and/or hypertension) had significantly (P < 0.001) elevated levels of total complement, C3 fraction and circulating complexes compared with the control group. Total complement and circulating complexes levels were most elevated in patients with a combination of diabetes and hypertension. Similarly, these patients had the highest frequency of antitissue antibodies. In summary, the parameters of humural immunity were more changed in patients with two risk factors (diabetes and hypertension) compared to patients with only one risk factor. It is possible that these immunological changes appeared earlier than clinical symptoms of atherosclerosis and they could be used as an early prognostic test for predisposition to atherosclerotic vascular complications.