We used a glioblastoma multiform (GBM) cell line to study the mechanism of cellular regulation of nitric oxide (NO) production. Our experiments indicate a confluent monolayer of GBM cells to release NO as measured through its oxidized NO2 form which gradually accumulates and reaches a peak by 7 to 10 days of culture. the addition of the L-arginine analogs L-NG-monomethyl-L-arginine and L-N omega-nitro-L-arginine and dexamethasone to the GBM cultures caused a substantial inhibition of NO production. The addition of monoclonal antibodies against IL-1 and TNF alpha to the cultures resulted in an inhibition of NO production, whereas the addition of anti-TGF beta monoclonal antibodies resulted in an increase in NO production. These findings suggest the presence of an autocrine regulatory mechanism for NO production in some tumor cell lines.