Lymph flow and lymphatic pressure fluctuations were measured in cannulated popliteal efferent lymphatics of the sheep. Five-minute intra-arterial infusions of norepinephrine (0.4 microgram/kg/min) produced up to fivefold increases in lymph flow and lymphatic contraction frequency. This effect was blocked by the alpha-antagonist phentolamine but not by the beta-antagonist propranolol. Isoproterenol (0.4 microgram/kg/min i.a.) inhibited flow. This effect was antagonized by propranolol. Acetylcholine (0.4 microgram/kg/min) had little effect on lymph flow. Since norepinephrine and isoproterenol respectively stimulate and inhibit lymphatic pumping activity in vitro, it is proposed that the effects of these agents on lymph flow and lymphatic contraction frequency in vivo are best explained by direct modulatory actions on the lymphatic smooth muscle pump.