4-Aminopyridine (4-AP) was shown to be able to induce histamine release from peritoneal mast cells (PMC) in mice and rats. Disodium cromoglycate (DSCG) 200 mg/kg sc in mice or DSCG (0.12 mmol/L) in vitro in rats inhibited histamine release induced by 4-AP from PMC, The release rate of histamine caused by 4-AP from PMC in mice administered with DSCG was 14.6±4.5%，with significant difference from the controls 48.8±4.3% (P<0.01). After preincubation of rat PMC with DSCG in medium, the release rate of histamine by 4-AP was 20.4±6.0%, significantly lower than that in the controls (50.0±6.0%) (P<0.01). These results have indicated that histamine release in response to 4-AP might be related to the blockade of K⁺ channels and that DSCG may be effective for alleviation of the adverse reactions due to histamine release after administration of 4-AP in clinical practice.