The effects of PGI2 and two analogs Iloprost and ZK 96480 were examined on isolated human pulmonary muscle preparations. High concentrations of these agents reduced the basal tone in all types of preparations. In addition, they relaxed tissues which had been maximally contracted with histamine (50 microM). PGI2 was more potent on pulmonary arterial muscle preparations (pD2 value: 6.33, n = 3) than on bronchial muscles. The relaxations induced by PGI2 in bronchial preparations were quite variable, that is, some tissues relaxed while others did not. The analogs also relaxed arterial preparations and the pD2 values were approximately the same (Iloprost: 7.42, n = 4 and ZK 96480: 7.48, n = 4). The isolated human pulmonary vascular preparations were approximately 10-fold more sensitive to the analogs than bronchial muscle preparations. In bronchial tissues we noted that the PGI2 relaxant effect was spontaneously reversed with time, an activity not observed with both analogs. A pretreatment of the bronchial tissues with indomethacin (1.7 microM) did not reduce the variations observed with PGI2 nor modify the transient relaxation observed with this agent. These data demonstrate that vascular tissues from the human lung are considerably more sensitive to these relaxant agonists than bronchial preparations.