1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1-25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.