Recent studies have shown that somatostatin modulates lymphocyte function, but the effects of somatostatin on macrophage function are not clearly defined. In the present study, peritoneal macrophages (Mluminal diameter) obtained from male rats were treated in vitro with somatostatin or octreotide and their effects on the release of hydrogen peroxide (H2O2), nitrite, and tumor necrosis factor (TNF) determined. Macrophages treated with somatostatin (10(-9) M to 10(-7) M) or octreotide (10(-8) M and 10(-7) M) released significantly greater amounts of PMA-stimulated H2O2 than did the untreated controls. In addition, 10(-9) M of somatostatin significantly enhanced PMA-stimulated H2O2 release by LPS-treated Mluminal diameter. Octreotide had no effect on H2O2 release by LPS-treated Mluminal diameter. At concentrations of 10(-14) M, 10(-13) M, or greater than 10(-8) M, somatostatin or octreotide suppressed nitrite release by Mluminal diameter. Somatostatin or octreotide did not affect nitrite release by LPS-treated Mluminal diameter. On the other hand, Mluminal diameter treated with 10(-11) M of somatostatin or octreotide released greater amounts of TNF than did the untreated controls. In contrast, TNF release by Mluminal diameter treated with 10(-9) M to 10(-5) M of somatostatin or 10(-7) M to 10(-5) M of octreotide was less than that of the controls. Anti-TNF antibody (1:1000) caused a reduction in the release of H2O2 and nitrite. These findings demonstrate that somatostatin and octreotide modulate the release of H2O2, nitric oxide, and TNF by Mluminal diameter depending on the concentration of hormones used.