The effect of supernatants of isolated lymph node cells exposed to insulin has been studied on the anaphylactoid reaction induced by dextran in the rat paw. Native supernatants derived from rat lymphocytes were shown to increase dextran response only from April to October, while in the intermediate period no potentiation was obtained. The supernatants were filtered through sephadex G-25, G-50, and G-100 gels. Pro-inflammatory activity was recovered in the void volume of sephadex G-25 or G-50 columns, while it ran with bovine serum albumin marker suggesting an approximate mol. wt. of 70-kilodalton. Potentiation was detectable in adrenalectomized rats from November through April. A fraction of the eluate recovered from sephadex G-25 gels in the range of 1- to 6-kilodalton was found to suppress dextran edema. Supernatants of calf lymph node cells with insulin were fractionated on DEAE-sephadex A-50 and yielded two distinct fractions, one with pro-inflammatory and the other with anti-inflammatory effect. These results suggest that insulin affects anaphylactoid reaction via the release of some lymphocyte mediators.