OBJECTIVE: Our purpose was to investigate whether uterine microvascular responses to human chorionic gonadotropin application depend on route of administration and estrous cycle day. STUDY DESIGN: One uterine horn was exteriorized in pentobarbital-anesthetized cycling and ovariectomized rats and superfused with Krebs solution. Uterine arterioles (64 ± 2.1 μm) were viewed by videomicroscopy. Diameters were measured during a 20-minute baseline period and for 60 minutes during human chorionic gonadotropin suffusion (20 IU/60 ml) or 60 minutes after intraperitoneal injection of 50 IU of human chorionic gonadotropin. Papaverine (100 μmol/L) suffusion maximally dilated the uterine arterioles (80 ± 2.6 μm). RESULTS: Suffusion of human chorionic gonadotropin–dilated arterioles on diestrus-1 (122% ± 2% baseline) and diestrus-2 (118% ± 4% baseline) but constricted arterioles on proestrus (78% ± 7% baseline). Intraperitoneal injection of human chorionic gonadotropin resulted in arteriolar constriction on diestrus-2 (76% ± 5% baseline) and proestrus (82% ± 3% baseline). Ovariectomy eliminated the effects of injected but not suffused human chorionic gonadotropin. All results are significant at p < 0.05. CONCLUSIONS: Results indicate estrous cycle day–dependent direct and indirect effects of human chorionic gonadotropin on the resistance of uterine arterioles. (Am J Obstet Gynecol 1997;176:150-7.)