The serum proteins composing the complement system play a role in defense against infection and in the generation of immune-mediated disorders. To examine this system three components of the complement system in diabetes have been measured--an element in the classic (antibody-mediated) pathway, C4; an element in the properdin (non-antibody) pathway, C3 activator; and an element common to both pathways, C3. The levels of all three are increased both in diabetics and in individuals with glucose intolerance. In the glucose intolerant subjects elevation occurred either with or without fasting hyperglycemia. The levels of all three complement components were found to be positively correlated with fasting plasma glucose in the glucose intolerant group. An increase of complement components with age was found in the overall study population, and in two individual groups. For this reason a further comparison was made between nondiabetics and diabetics on the basis of age; the diabetic complement increase was still detectable. The levels of individual complement components were correlated with each other in both diabetic and nondiabetic groups. An inverse correlation was found between C3 activator and albumin level. The elevation of all complement components was found to be unrelated to the presence or severity of diabetic microvascular sequelae. The simultaneous development of complement elevation and glucose intolerance strongly suggests a metabolic basis for the increase in its components while the lack of association of complement elevation with diabetic sequelae argues against a role for complement in the pathogenesis of diabetic microangiopathy.