The objective of this study was to investigate the effects of heat shock (HS) treatment and geldanamycin (GA) on the release of arachidonic acid (AA) from human peripheral blood mononuclear cells (PBMC), monocytes and lymphocytes. Mononuclear cells prepared from blood of healthy subjects were preincubated with (3)H-AA. The release of (3)H-AA incorporated into the membrane was studied after pretreatment of cells by HS (43 degrees C, 1 h) and GA. The activation of AA producing enzymes was achieved by the addition of phorbol 12-myristate 13-acetate (PMA) or by the combination of PMA+calcium ionophore A-23187. Treatment of cells by HS inhibited the release of AA. Furthermore, the release of AA by PBMC was dose dependently inhibited by GA. The combination of treatments by HS and GA augmented the inhibition of AA release. The HS response involves a diminished release of AA from PBMC. The inhibitory effect of GA on the AA release is a new element in the antiinflammatory pharmacological ability of this drug.