The effect of sera from male type 2 (non-insulin dependent) diabetics in variable metabolic control on the proliferation of, and on the synthesis of hyaluronic acid and collagen in human aortic smooth muscle cells (HSMCs) in culture was studied. Pooled sera from diabetics in poor metabolic control either with or without antidiabetic drugs stimulated the proliferation and hyaluronic acid synthesis of the cells more than did pooled serum from healthy controls. On the other hand, pooled serum from diabetics in good metabolic control did not have a higher stimulatory effect on the growth of HSMCs than pooled control serum. Indeed, it increased the synthesis of hyaluronic acid similarly as did the pooled serum from poorly controlled diabetics. The synthesis of collagen was not affected by pooled diabetic sera. When the effects of 14 male diabetic sera were individually measured using the same functions of HSMCs, metabolic control of diabetes did not correlate with various activities of diabetic sera on HSMCs. The results show that sera of type 2 diabetics contain factors affecting the functions of HSMCs. The activity of the factors on cell proliferation is related to some extent to the degree of glycemic control, as shown in experiments with serum pools, but experiments with individual sera show that other serum properties unrelated to the metabolic control of diabetes are also of importance.