In patients with insulin-dependent (Type 1) diabetes mellitus abnormal endothelial cell proliferation was considered as one of the possible explanations for the occurrence of retinopathy. Since monocyte-derived factors have been proposed to be involved in endothelial cell growth regulations we have measured the effect of monocyte-conditioned medium (MO-CM) on endothelial cell proliferation and the production of Tumor necrosis factor alpha and interleukin 1-beta, cytokines known to alter endothelial cell functions. The effect of MO-CM in 20 patients with Type 1 diabetes and proliferative retinopathy on endothelial cell proliferation estimated on [3H] thymidine incorporation, was lower to that observed with the MO-CM in 20 normal controls but the difference did not reach the statistical level of significance. The basal tumor necrosis factor alpha secretion expressed by monocytes was significantly lower in the MO-CM from Type 1 diabetes patients (median: 0.49, range 0.13-2.86 ng/10(6) monocytes) than in the MO-CM from the control subjects (median: 1.84, range: 0.13-7 ng-10(6) monocytes) p < 0.02. The increase in interleukin 1-beta and in tumor necrosis factor alpha production after lipopolysaccharide stimulation were similar in the 2 groups. A low basal tumor necrosis factor production per monocyte may contribute to the development of the diabetic complications as it is involved in several cellular regulation processes.