Since intrinsic cellular abnormalities have previously have reported in diabetes mellitus, skin fibroblasts from patients with insulin-dependent diabetes and non-insulin-dependent diabetes, and from age-matched young and old controls, were examined for stimulation by insulin (4--4000 ng/ml) of glucose uptake, leucine incorporation into protein, and uridine incorporation into RNA. No differences in insulin-stimulated glucose uptake were seen between donor types. At 40 and 400 ng/ml, insulin did not stimulate as much leucine incorporation into protein in insulin-dependent diabetics as in young controls (p less than 0.05) and at 4000 ng/ml, less insulin-stimulated leucine incorporation was seen in insulin-dependent diabetics than in young controls or non-insulin dependent diabetics (p less than 0.01). Lower insulin-simulated uridine incorporation into RNA in old controls than in other cell lines appeared to be largely secondary to a two-fold increase in basal incorporation in these old controls. These results provide additional evidence for intrinsic cellular abnormalities in diabetes mellitus. Whether the differences in basal or insulin-stimulated response between fibroblasts of different donor types are attributable to alterations in protein or RNA synthesis, metabolite pool size or turnover have yet to be determined.