To assess the possible involvement of humoral immunity in diffuse atherosclerosis, IgG, IgA, IgM, C3 and C4 were measured in the sera of 23 atherosclerotic subjects (at least 3 stenoses greater than 75% in the arteries of the limbs and neck, as assessed by panangiography) and of 20 controls (possible stenoses less than 40% documented by arteriography of the aortic arch and epi-aortic branches and "normal" response to exercise stress testing and Doppler ultrasonography of the arteries of the lower limbs). Age (59-69) and sex distribution did not differ significantly in the 2 groups. The following serum concentrations were higher in the atherosclerotic subjects than in the controls: C4 (28.7 +/- 6.5 (1 SD) vs. 23.4 +/- 3.8 mg/dl; P = 0.0013); IgA (323.3 +/- 155.0 vs. 210.3 +/- 87.9 mg/dl; P = 0.0020); and C3 (126.3 +/- 16.9 vs. 111.0 +/- 18.9 mg/dl; P = 0.0109). To assess whether these parameters were independently associated with atherosclerosis, a multiple logistic regression was performed, also including other variables which differed between the atherosclerotic group and the control group with P values less than 0.20 (cigarette smoking, arterial hypertension, body mass index, serum HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, serum triglycerides, IgG and IgM). In multivariate analysis only IgA (P = 0.0012), C4 (P = 0.0072), cigarette smoking (P = 0.0141) and serum triglycerides (P = 0.0177) were independently associated with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)