When monocytes are activated with endotoxin (lipopolysaccharide [LPS]), they make and release several mediators, including interleukin-1 beta (IL-1 beta). This study was undertaken to investigate the role of glucose in IL-1 beta production by these cells. IL-1 beta was produced in a dose-dependent manner to glucose concentration in the culture medium. The uptake of (3H)2-deoxyglucose in monocytes was stimulated by LPS 1,554% after 10 minutes, 6,095% after 2 hours, then gradually declined after 4 hours of incubation. The inhibition of the uptake of (3H)2-deoxyglucose by either 10 microM cytochalasin B or phloretin, added at the time of monocyte activation, was accompanied by significant reduction in ATP/ADP ratio and the inhibition of the production of IL-1 beta by activated monocytes. The synthesis of total protein did not change in monocytes activated in the absence of glucose in the culture medium, nor in the presence of either 10 microM cytochalasin B or phloretin. The export of IL-1 beta from LPS-activated monocytes was not inhibited by either 10 microM cytochalasin B or phloretin, nor in the absence of glucose in the culture medium. These data suggest that 1) glucose is required for LPS-induced IL-1 beta production by monocytes; 2) glucose is the major source of ATP for IL-1 beta production; 3) glucose transporter (GLUT 1) does not control the export of IL-1 beta.