14-deoxyandrographolide (DA) and 14-deoxy-11,12-didehydroandrographolide (DDA) are two diterpenoids isolated from A. paniculata, a popular folk medicine used as an antihypertensive drug in Malaysia. We have previously reported that DDA exhibited a greater hypotensive effect in anaesthetized rats and a vasorelaxant activity in isolated rat aorta, compared with DA. Their vasorelaxant activities were mediated through the activation of the enzymes, nitric oxide synthase (NOS) and guanylyl cyclase. The present study demonstrated that both DA and DDA stimulated nitric oxide (NO) release from human endothelial cells. DDA compared with DA caused a greater production of NO; this is in line with the finding of the earlier study that the vasorelaxant effect of DDA was more dependent on endothelium than DA.