Higher basal 2-deoxy-d-glucose uptake in rheumatoid synovial cells than in non-rheumatoid synovial cells, was found to be associated with an increased interleukin-1β (IL-1β) secretion (respectively 850 ± 238 vs. 8.3 ± 2.4 pg/24 h/105 cells, mean ± S.E.M.). When exogenous human recombinant IL-1β was added to cultures, a marked stimulation of 2-deoxy-d-glucose uptake was performed by both human synovial cultured cells, in a time-dependent and dose-dependent manner (IL-1β0–100 ng/ml). In non-rheumatoid synoviocytes, stimulation occurred 1–3 h following the addition of 1 ng/ml interleukin-1β and increased up to 24 hours (respectively +150% and +261.4% after 6 and 24 hours association time). Rheumatoid synovial cells were less sensitive to 1 ng/ml IL-1β (respectively +80% and +146.4%). IL-1β increased significantly the V max for 2-deoxy-d-glycose uptake by synovial cells, with no change in the K m. This effect was protein synthesis-dependent, and not secondary to prostaglandin E2 synthesis or cell growth. IL-1β possesses an important effect on glucose homeostasis in synovial cells, which could be indirect and/or regulated by the presence of natural inhibitors.