Although the capillary wall represents an active interface between blood and tissue, the potential role of the capillary in blood flow control has not been determined. The goals were (i) to establish the presence of the capillary sensing and communication phenomenon (Dietrich and Tyml, Microvasc. Res. 43, 87-99, 1992) in mammalian microvasculature and (ii) to determine the relative sensitivity of the capillary and the arteriole to locally applied vasoactive agents. Using intravital video microscopy, norepinephrine (NE; 10(-7)-3 x 10(-3) M), acetylcholine (ACh; 10(-4)-10(-2) M), or bradykinin (BK; 10(-9)-10(-3) M) was applied via micropipettes on capillaries (300 mu m downstream from feeding arterioles) or on arterioles, at the surface of the extensor digitorum longus muscle of anesthetized rats. Red blood cell velocity (V-RBC) in capillaries and arteriolar diameters was measured from video recordings. The overall control V-RBC and control diameter were 190 mu m/sec and 8.3 mu m, respectively. NE applied on the capillary caused a dose-dependent reduction in V-RBC (UP to 100%, i.e., 0 mu m/sec) via a constriction of the feeding arteriole. Both ACh and BK applied on the capillary caused a dose-dependent increase in V-RBC (up to 115%) via arteriolar dilation. Based on two different approaches, these responses could not be explained in terms of diffusion of agents from capillary to the arteriole. When testing for the relative sensitivity of the arteriole and the capillary, application of NE and ACh on arterioles caused V-RBC and diameter responses similar to those of capillary stimulations. When testing for the speed of response in these two microvessels, the time of noticeable V-RBC change after NE (i.e., 10% from control) was also similar. We concluded that (i) the rat skeletal muscle capillary could respond to a variety of locally applied materials and (ii) the capillary could have as profound an effect on microvascular flow as the arteriole. Thus capillary could have the potential to participate in microvascular flow control. (C) 1997 Academic Press.