An intravenous glucose tolerance test was performed in 45 untreated patients with active inflammatory rheumatoid arthritis and in age- and sex-matched healthy subjects. The mean k value in the patients, which correlated to the inflammatory activity, was 1.0 +/- 0.05 (SEM), which was significantly lower (P less than .001) than in the controls (1.8 +/- 0.09). The basal serum insulin concentration and the maximum insulin response to glucose loading were significantly higher (P less than .001 and P less than .01, respectively) in the patient group. The patients had a normal basal concentration of growth hormone in the serum, but during glucose infusion the concentration increased. The plasma glucagon level was significantly lower than in the controls (P less than .001). The urinary output of cortisol and catecholamines was normal. It is concluded that impaired glucose handling in active chronic inflammatory disease cannot be explained as a stress reaction but may be due to peripheral insulin resistance mediated by the inflammatory process. A paradoxical increase in growth hormone secretion during glucose infusion may suggest that this hormone is one factor that influences glucose handling in chronic inflammation. The pathophysiologic relevance of altered glucose metabolism and enhanced insulin secretion is uncertain but may reflect a possible link with the proposedly increased risk of atherosclerotic cardiovascular disease in rheumatoid arthritis.