(1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide. With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon. Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients.