Chronic microcirculatory alterations produced by prolonged use of a vasoactive drug were repeatedly observed in the same skeletal muscle vessels of the dorsal microcirculatory chamber. Arterioles and venules with diameters averaging from 70 to 90 /tm, the size range contributing most to peripheral vascular resistance, were measured daily for 6 days to determine differences in diameter, tortuosity, and number of branches. Hydralazine was given as a subcutaneous pellet (2.5 mg), with a release life of 21 days. Hydralazine caused a 39% dilation in arterioles of Wistar-Kyoto rats (WKY) at 3 hours but only an 8% dilation in those of spontaneously hypertensive rats (SHR). At 6 hours, arterioles In both groups were similarly dilated (30–33%). Beyond 6 hours, both SHR and WKY arterioles returned to their prehydralazine control diameter, even though arterial pressure was still reduced. By Day 6, in WKY, but not SHR, there was an increase in the tortuosity of arterioles and a tendency for an hicrease in their number. Venous diameter was also increased on Day 6, consistent with the fluid retention effect of hydralazine. These data indicate that some so-called vasodilators may cause long-term alterations in growth of vessels rather than an increase in vessel caliber.