Macrophages have been show to be of importance in three areas of pathology in the diabetic state: (a) in the destruction of the beta cells of the pancreas; (b) in the pathogenesis of the microvascular lesions; and (c) in the atherosclerotic lesion which is a common complication of diabetes. However, there is only scanty information on the behavior of the macrophage in the hyperglycemic environment. The present study investigates the growth of WEHI-3 monocytes/macrophages and the proliferative response of splenic macrophages to colony stimulating factor-1 when cultured in media containing high glucose concentrations. The results of the study show that hyperglycemia increases the proliferation of these macrophages; this effect is not mediated by the effect of osmolality since mannitol and L-glucose failed to produce a similar result. These findings suggest that alterations of macrophage physiology may be an important component of the diabetic state; such alterations may have a role in the production of some of the lesions found in diabetes mellitus.