We demonstrated previously that 10(-5)M micellar solution of lysophosphatidylcholine (LPC) produced relaxation of rabbit thoracic aorta in a dose-dependent manner. It was also noticed that histamine (HA)-precontracted strips relaxed spontaneously in the absence of LPC. We now measured the cyclic GMP changes during these two types of relaxation. Results indicate that while LPC-induced relaxation was mediated through cyclic GMP, spontaneous relaxation was not. The vasodilating effect of LPC was not due to its interference with cellular viability by solubilizing the membrane, because repeated additions of LPC produced identical degrees of relaxation and after three consecutive additions of LPC, the strips continued to relax to the same degree with acetylcholine (Ach) demonstrating the functional integrity of the endothelium. LPC/Cholesterol dispersions (1:0.5 mole percent) relaxed the strips to the same extent as the micellar solution of LPC, while 1:1 mole percent did not. The results stress the role of cyclic GMP in LPC-induced relaxation. They further suggest that LPC/Cholesterol ratio may determine the availability of LPC and regulate LPC-mediated processes.