Glucose metabolism was studied after an intravenous glucose loading in normal-weighted, previously untreated patients (n = 14) with active rheumatoid arthritis (RA). The patients displayed an enhanced insulin response and impaired glucose handling compared with healthy controls (P less than .001). The insulin sensitivity, measured as the glucose utilization rate during steady state of euglycemia (M) was significantly decreased (P less than .01) among the patients compared to the controls (5.5 +/- 1.9 mg/kg BW/min [mean +/- SD] and 7.2 +/- 1.2, respectively). The corresponding values for the metabolic clearance rate (MCR) were 5.8 +/- 0.6 mL/kg BW/min and 8.2 +/- 0.4, respectively (P less than .01). In the patient group the k value correlated with the peripheral insulin sensitivity (P less than .01), which, in turn, was inversely related to the acute phase reaction (P less than .05). During 1 week of potent anti-inflammatory treatment with corticosteroids (prednisolone 20 mg daily) the k value improved P less than .001), the insulin sensitivity tended to improve and the insulin response increased (P less than .001) after an intravenous glucose loading. Five patients who had a remission of their disease on sulphasalazine as antirheumatic therapy were reexamined. A normalization of the inflammatory activity as well as the glucose handling and insulin sensitivity was achieved. The data obtained indicate that impaired glucose handling in active RA is related to insulin resistance. The linkage between inflammatory indices and glucose metabolism might reflect a special consequence of inflammation, but the influence of nonspecific disease manifestations, ie, malnutrition, inactivity, and myopenia, has to be considered.