Eosinophils are believed to contribute proinflammatory effects in allergic inflammation, including asthma. The cytokines such as hematopoietins, interleukin-5 (IL-5), IL-3 and GM-CSF have been shown to stimulate production of eosinophils in the bone marrow, and the same cytokines inhibit eosinophilic apoptosis and prolong survival when eosinophils are cultured. In allergic individuals, large numbers of eosinophils are accumulated and release activated oxygen and toxic granule-derived proteins such as major basic protein and eosinophil cationic protein. Consequently, agents that inhibit the prolongation of eosinophil survival will be another candidate for development of drugs to treat bronchial asthma. In the course of our screening for inhibitors of IL-5 mediated prolongation of eosinophil survival, a fungus, Aspergillus ustus (Bain.) Thorn & Church TC 1118 was found to produce three novel isoquinoline alkaloids, designated as TMC-120A (1), B (2) and C (3). We report here the production, isolation and biological activities of TMC-120A, B and C, and their derivatives. TMC-120B (2) showed moderate inhibitory activity against the IL-5 mediated prolongation of eosinophil survival (IC50=2.0 μM), but TMC-120A (1), TMC-120C (3), and their reductive analogs (4, 5) were less active than TMC-120B or inactive. These results suggested that the α,β-unsaturated ketone of TMC-120B played an important role in its activity, possibly involving the alkylation of biological nucleophiles via a Michael-type addition. Additionally, TMC-120B showed no cytotoxicity against human leukemia HL-60 cells at a concentration of 42 μM.