A link between glucose transport and apoptosis was suggested. We studied the mechanisms of glucose transport in human eosinophils by means of the uptake of the positron emitting analogue, 18Fluoro-2-Deoxyglucose (FDG) and apoptosis by means of flow cytometry. FDG uptake was inhibited by antibodies to GLUT1, 3 and 4 and by cytochalasin B. The anti-apoptotic principles IL-5, GM-CSF, IL-3 enhanced the uptake, whereas the apoptosis-inducing principles anti-CD95 (anti-Fas) and exposure to serum-coated Sephadex particles caused a reduction. Also TNF-alpha enhanced the uptake. Other cytokines such as IL-2, IL-4, IL-8, RANTES and MCP-3 had no effect on the glucose uptake. 2-Deoxyglucose, antibodies to GLUT4 and CD95 induced apoptosis. The basal FDG-uptake was unaffected by PKC inhibitors Ro-31-8220, Gö-6983 and Gö-6976, whereas the latter inhibited the IL-5-enhanced uptake possibly due to the inhibition of PKC(mu). Protein tyrosine kinase and PI-3 kinase inhibitors inhibited IL-5-enhanced FDG-uptake only. In contrast MEK inhibitors inhibited the basal uptake only. Inhibitors of p38 MAPkinase inhibited both basal and IL-5 enhanced uptake. We conclude that glucose uptake in eosinophils is governed by specific intracellular mechanisms involving mobilization of GLUTs, Ca2+ and the activation of the MAP kinase pathway and that the IL-5-enhanced uptake uniquely seems to involve PKC(mu) activity. Our results suggest a close link between apoptosis and glucose transport in human eosinophils.