The selectivity of endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) on smooth muscle relaxation was examined and compared. EDRF released from was examined and compared. EDRF released from bovine pulmonary arterial endothelium (BPAE) in culture and NO were superfused over vascular, tracheal, gastrointestinal and uterine smooth muscle. EDRF relaxed vascular smooth muscle but not tracheal, gastrointestinal or uterine smooth muscle. NO relaxed vascular and gastrointestinal smooth muscle but not tracheal or uterine smooth muscle. There was a differential selectivity between the relaxant effect of EDRF and NO on smooth muscle.